Volume 53, No. 8/2015(August)
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Original
Impact of pharmacist interventions on rational prophylactic antibiotic use and cost saving in elective cesarean section
Jingwen Wang, Mohan Dong, Yang Lu, Xian Zhao, Xin Li, and Aidong Wen
Price
42.00 $
Page No. 605
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 8/2015 (605-615)
Impact of pharmacist interventions on rational prophylactic antibiotic use and cost saving in elective cesarean section
Jingwen Wang1*, Mohan Dong1*, Yang Lu1, Xian Zhao1, Xin Li2, and Aidong Wen1
1Department of Pharmacy, Xijing Hospital, the Fourth Military Medical University, Xi’an, and 2Department of Clinical Pharmacy, School of Pharmacy, Nanjing Medical University, Nanjing, China
Objectives: To assess the impact of pharmacist interventions on rational use of prophylactic antibiotics and cost saving in elective cesarean section and the economic outcomes of implementing pharmacist interventions. Methods: A pre-to-post intervention design was applied to the practices of prophylactic antibiotic use in the department of gynecology and obstetrics in a Chinese tertiary hospital. Patients admitted during a 3-month period from June to August 2012 and during that from October to December 2012 undergoing elective cesarean section were assigned to the pre-intervention and the post-intervention group, respectively. Pharmacist interventions were performed in the post-intervention group, including obstetrician education, realtime monitoring of clinical records and making recommendations to obstetricians on prophylactic antibiotic prescription based on the criteria set at the beginning of the study. Data from the two groups were then compared to evaluate the outcomes of pharmacist interventions. Cost-outcome analysis was performed to determine the economic effect of implementing pharmacist interventions in preoperative antibiotic prophylaxis. Results: Pharmacist interventions led to significant reductions in antibiotic usage cost/patient-day (p < 0.001), mean antibiotic cost (p < 0.001), mean tota drug cost (p < 0.001), mean total hospitalization cost (p < 0.001), the duration of prophylaxis antibiotics (p < 0.001) and a significant increase by 19.29% in the percentage of cases adhering to all of the four criteria (p < 0.001). The ratio of the saving in antibiotic use to the cost of pharmacist time was 27.23 : 1 and the net cost benefit was $65,255.84. Conclusion: This study provides evidence that pharmacist interventions promoted rational use of prophylactic antibiotics and substantial cost saving in elective cesarean section.
*These authors contributed equally to this work.Correspondence to:
Prof. Xin Li, PhD
Department of Clinical Pharmacy
School of Pharmacy, Nanjing Medical University
101 Longmian Avenue, Nanjing 211166, China
or
Prof. Aidong Wen, PhD
Department of Pharmacy, Xijing Hospital
The Fourth Military Medical University
15 West Changle Road, Xi’an 710032, China
Email: [email protected] or [email protected]
Original
Current smoking is an independent risk factor for new-onset diabetes mellitus during highdose glucocorticoid treatment
Takao Sugiyama, Toyohiko Sugimoto, Sawako Suzuki, Yuta Sato, Tomoaki Tanaka, and Ichiro Tatsuno
Price
42.00 $
Page No. 616
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 8/2015 (616-620)
Current smoking is an independent risk factor for new-onset diabetes mellitus during highdose glucocorticoid treatment
Takao Sugiyama1, Toyohiko Sugimoto2, Sawako Suzuki2, Yuta Sato3, Tomoaki Tanaka2, and Ichiro Tatsuno3
1Department of Rheumatology, National Hospital Organization Shimoshizu National Hospital, Yotsukaido, 2Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Chiba, and 3Center for Diabetes, Metabolism and Endocrinology, Toho University Sakura Medical Center, Sakura, Japan
Aims/Introduction: Although high-dose glucocorticoids have been reported to cause new-onset diabetes mellitus (glucocorticoid-induced diabetes mellitus), its risk factors have remained to be determined. We investigated the risk factors related to glucocorticoid-induced diabetes mellitus diagnosed within 2 months after the high-dose treatment (newly treated with an initial high dose of > 20 mg prednisolone (PSL) equivalent per day for at least more than 6 months) in collagen vascular diseases. Methods: A total of 2,631 patients with collagen vascular diseases was registered between 1986 and 2006 in the Chiba-Shimoshizu Rheumatic Cohort. We analyzed 681 patients newly treated with high-dose glucocorticoid who did not have diabetes mellitus and/or its previous diagnosis (age: 46.3 ± 16.7 years, PSL dose: 40.0 ± 14.1 mg/day). Glucocorticoid-induced diabetes mellitus was diagnosed by two or more glucose measurements in patients with fasting glycaemia ≥ 7 mmol/L and 120 minutes post-load glycaemia ≥ 11.1 mmol/L. Results: Glucocorticoid-induced diabetes mellitus was observed in 26.3% of patients, and the glucocorticoid-induced diabetes mellitus group had higher age, higher BMI, lower rates of females and systemic lupus erythematosus, higher rates of smoking, alcohol use, and microscopic polyangiitis. Multivariate logistic regression analysis demonstrated that the risk of glucocorticoid-induced diabetes mellitus was independently higher in every 10-year increment of initial age with adjusted odds ratio (OR) 1.556 (95% confidence interval: 1.359 – 1.783), in every 1 kg/m2 increment of BMI with OR 1.062 (1.002 – 1.124), in current smoking with OR 1.664 (1.057 – 2.622), and in every 10 mg increment of initial dose of prednisolone with OR 1.250 (1.074 – 1.454). Conclusions: High-dose glucocorticoids caused diabetes mellitus with high prevalence within a short period, and current smokers should be considered at higher risk of glucocorticoidinduced diabetes mellitus in addition to age, BMI, and initial dose.Correspondence to:
Ichiro Tatsuno, MD, PhD
Center for Diabetes, Metabolism and Endocrinology
Toho University Sakura Medical Center
564-1 Shimoshizu, Sakura-City, Chiba 285-8741, Japan
Email: [email protected]
Original
Evidence supporting the need for considering the effects of smoking on drug disposition and effectiveness in medication practices: a systematic narrative review
Hyun Soon Sohn, Hyunah Kim, Im-Sook Song, Eunjeong Lim, Mihwa Kwon, Ji-Hye Ha, and Jin-Won Kwon
Price
42.00 $
Page No. 621
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 8/2015 (621-634)
Evidence supporting the need for considering the effects of smoking on drug disposition and effectiveness in medication practices: a systematic narrative review
Hyun Soon Sohn1*, Hyunah Kim2*, Im-Sook Song3, Eunjeong Lim3, Mihwa Kwon3, Ji-Hye Ha4, and Jin-Won Kwon3
1Graduate School of Clinical Pharmacy, CHA University, Gyeonggi-do, 2College of Pharmacy, Sookmyung Women’s University, Seoul, 3College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, and 4Clinical Research Division, National Institute of Food and Drug Safety Evaluation (NIFDS), Chungcheongbuk-do, South Korea
This study was conducted to provide a narrative overview of interactions between smoking and drug effectiveness/ pharmacokinetics. Database searches were performed to identify review articles published prior to March 10, 2013. Eligible articles reporting altered pharmacokinetic profiles, drug response, or adverse drug effects due to drug-smoking interactions were selected. Information on mechanism of action and clinical effects from the selected articles (n = 83) were summarized by therapeutic drug class. For cardiovascular drugs, smoking effects were variable. Smoking reduced aspirin response but increased clopidogrel response by increasing active metabolites. Warfarin, which has a narrow therapeutic range, required dosage adjustment in smokers due to its rapid clearance. Smoking is a risk factor for respiratory disease, leading to a lower response to corticosteroid and requiring increased doses or additional drugs. Higher doses of theophylline and some antipsychotics, which are mainly metabolized by CYP1A2, are required to reach an optimal plasma concentration in smokers. Smoking is also a risk factor for cancer, especially for lung cancer. Erlotinib or gefitinib are epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for lung cancer and showed lower anticancer effects in smokers. This summary of the interactions between smoking and drug pharmacological properties will aid healthcare professionals in providing patients with appropriate drug therapies, and emphasizes the need for considering smoking status as a patient factor in the clinical setting.
*Sohn HS and Kim H equally contributed as co-first authors.Correspondence to:
Jin-Won Kwon, MPH, PhD
College of Pharmacy and Research Institute of Pharmaceutical Sciences
Kyungpook National University
80 Daehak-ro, Buk-gu, Daegu 702-701, South Korea
Email: [email protected]
Original
Pitavastatin therapy in polymedicated patients is associated with a low risk of drug-drug interactions: analysis of real-world and phase 3 clinical trial data
Masahiko Gosho, Masaya Tanahashi, Neil Hounslow, and Tamio Teramoto
Price
42.00 $
Page No. 635
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 8/2015 (635-646)
Pitavastatin therapy in polymedicated patients is associated with a low risk of drug-drug interactions: analysis of real-world and phase 3 clinical trial data
Masahiko Gosho1, Masaya Tanahashi2, Neil Hounslow3, and Tamio Teramoto4
1Unit of Biostatistics, Advanced Medical Research Center, Aichi Medical University, Japan, 2Clinical Data Science Department, Kowa Company, Ltd., Japan, 3Kowa Research Europe Ltd, Wokingham, UK, and 4Teikyo Academic Research Center, Teikyo University, Japan
Objectives: Medications that interact with the pathways responsible for statin metabolism may increase the risk of statin-associated myalgia. Pharmacokinetic studies show that pitavastatin is carried into the liver by a range of transporters and is minimally metabolized by cytochrome P450 in healthy volunteers, indicating a reduced potential for drug-drug interactions (DDIs). This post hoc analysis investigates the incidence of adverse events in patients receiving pitavastatin with concomitant medication in two large data sets. Methods: The largest pitavastatin patient data sets are the LIVALO Effectiveness and Safety (LIVES) postmarketing surveillance study in Japan (n = 19,925) and the European phase 3 clinical trial program (n = 2,396). Adverse events were classified according to the Medical Dictionary for Regulatory Activities (Med-DRA) and whether they occurred in patients taking medications that interact with hepatocyte organic anion-transporting polypeptide or cytochrome P450 (CYP) isoenzyme pathways. Results: Concomitant administration of pitavastatin with other medications was not associated with clinically significant increases in the incidence of adverse drug reactions (ADRs), even when given with medications that interact with CYP2C9, responsible for the minimal CYP metabolism of pitavastatin. There was a significant interaction with biguanides in LIVES, but this was associated with a reduced risk of muscle ADRs. Conclusion: In clinical trials, pitavastatin is associated with a low incidence of adverse events related to DDIs, consistent with data from healthy volunteers. Prescribing a metabolically stable statin, such as pitavastatin, may improve patient adherence to medication, thus facilitating the attainment of lipid targets and reducing cardiovascular risk.Correspondence to:
Tamio Teramoto, MD
Teikyo Academic Research Center
Teikyo University
2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan
Email: [email protected]
Original
CYP3A4*1G regulates CYP3A4 intron 10 enhancer and promoter activity in an allelicdependent manner
Weihong Yang, Dengzhi Zhao, Shengna Han, Zengyuan Tian, Liang Yan, Guoqiang Zhao, Quancheng Kan, Wei Zhang, and Lirong Zhang
Price
42.00 $
Page No. 647
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 8/2015 (647-657)
CYP3A4*1G regulates CYP3A4 intron 10 enhancer and promoter activity in an allelicdependent manner
Weihong Yang1, Dengzhi Zhao2, Shengna Han1, Zengyuan Tian3, Liang Yan1, Guoqiang Zhao1, Quancheng Kan4, Wei Zhang4, and Lirong Zhang1
1School of Basic Medical Sciences, Zhengzhou University, 2Yi He Hospital, Zhengzhou People’s Hospital, 3School of Life Sciences, Zhengzhou University, and 4The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Objective: CYP3A4*1G (G > A) in human CYP3A4 intron 10 is associated with therapeutic effects of CYP3A4-metabolized drugs. The aim of this study was to predict its function in the regulation of CYP3A4 expression. Methods: Functional analysis of the CYP3A4*1G allele was performed using bioinformatic methods and enhancer or promoter reporter assays in HepG2 cells. Results: Transcription regulatory elements like CAATboxes, TATA-boxes, Sp1, SMARCA3.01, and Box II-like sequence were present in the intron 10 of CYP3A4. SMARCA3.01 and Box II-like sequence were responsible for differential binding of transcription factors on the CYP3A4*1G allele. In CYP3A4*1G, the G allele enhanced expression of the CYP3A4 promoter in a position-dependent and orientation-dependent manner, however, the A allele enhanced expression of the CYP3A4 promoter in a position-independent and orientation-independent manner. In addition, the G allele and the A allele both displayed strong transcriptional activation, but the latter showed higher promoter activity than the former. Also, the A allele showed greater activity than the CYP3A4 promoter. Conclusion: These results in vitro suggest that CYP3A4*1G regulates CYP3A4 intron 10 enhancer and promoter activity in an allelic-dependent manner.Correspondence to:
Li-Rong Zhang and Prof. Wei Zhang, MD
Department of Pharmacology, School of Medicine
Zhengzhou University
100 Science Road, Zhengzhou 450001, China
Email: [email protected] and [email protected]
Original
Population pharmacokinetics and safety of eptifibatide in healthy Chinese volunteers and simulations on the dose regimens approved for a Western population
Xi-pei Wang, Zhi-ling Zhou, Min Yang, Li-ping Mai, Zhi-jie Zheng, Guo-dong He, Yue-heng Wu, Qiu-xiong Lin, Zhi-xin Shan, and Xi-yong Yu
Price
42.00 $
Page No. 658
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 8/2015 (658-666)
Population pharmacokinetics and safety of eptifibatide in healthy Chinese volunteers and simulations on the dose regimens approved for a Western population
Xi-pei Wang1*, Zhi-ling Zhou2*, Min Yang1,3*, Li-ping Mai1, Zhi-jie Zheng1, Guo-dong He1, Yue-heng Wu1, Qiu-xiong Lin1, Zhi-xin Shan1, and Xi-yong Yu1
1Research Center of Medical Sciences, 2Scientific Research and Education Department, and 3Department of Pharmacy, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
Objective: This study was designed to evaluate the pharmacokinetics (PK) and safety of eptifibatide in healthy Chinese volunteers and provide information for the further study in the Chinese population. Methods: 30 healthy volunteers (15 male) were enrolled in the study and divided into three dose groups (45 μg×kg–1, 90 μg×kg–1, and 180 μg×kg–1). Plasma and urine samples were drawn after one single-bolus administration and measured by LC-MS/MS. The plasma and urine data were analyzed simultaneously by the population approach using the NONMEM software and evaluated by the visual predicted check (VPC) and bootstraping. The PK profiles of dose regimens approved for a Western population in the Chinese population were simulated. Results: A two-compartment model adequately described the PK profiles of eptifibatide. The clearance (CL) and the distribution volume (V1) of the central compartment were 0.128 L×h–1×kg–1and 0.175 L×kg–1, respectively. The clearance (Q) and V2 of the peripheral compartment were 0.0988 L×h–1×kg–1 and 0.147 L×kg–1, respectively. The elimination fraction from plasma to urine (F0) was 17.2%. No covariates were found to have a significant effect. Inter-individual variabilites were all within 33.9%. The VPC plots and bootstrap results indicated good precision and prediction of the model. The simulations of the approved regimens in the Chinese population showed much lower steady-state concentrations than the target concentration obtained from the Western clinical trials. No severe safety events were found in this study. Conclusions: The PK model of eptifibatide was established and could provide PK information for further studies in the Chinese population.Correspondence to:
Xi-Yong Yu, MD, PhD
Guangdong General Hospital Medical Research Center
Guangdong Academy of Medical Sciences
106 Zhongshan 2nd Road, Guangzhou 510080, China
Email: [email protected]
Original
Comparison of pharmacokinetics and uric acid lowering effect between two different strength febuxostat formulations (80 mg vs. 40 mg) in healthy subjects
Kyoung-Ah Kim and Ji-Young Park
Price
42.00 $
Page No. 667
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 8/2015 (667-673)
Comparison of pharmacokinetics and uric acid lowering effect between two different strength febuxostat formulations (80 mg vs. 40 mg) in healthy subjects
Kyoung-Ah Kim and Ji-Young Park
Department of Clinical Pharmacology and Toxicology, Anam Hospital, University College of Medicine, Seoul, Korea
Objective: Febuxostat is a selective inhibitor of xanthine oxidase, which is used to manage hyperuricemia in patients with gout. The objective of the study was to compare the pharmacokinetics of two different strength of febuxostat formulations (80 mg and 40 mg). Methods: A randomized, single-dose, open-label, two-period, two-sequence crossover study with a 7-day washout period was conducted in 30 healthy male subjects. Participants received either reference (1 × 80 mg) or test (2 × 40 mg) formulations during the first period and the alternative formulation during the second period. Plasma samples for the drug analysis were collected up to 24 hours after treatment. Results: All pharmacokinetic parameters were comparable between the two formulations The observed mean Cmax, AUClast, and AUC∞ values for the reference formulation were 3,670 ng/mL, 12,086 ng×h/mL, and 12,880 ng×h/mL, respectively. Corresponding values for the test formulation were 4,108 ng/mL, 12,689 ng×h/mL, and 13,278 ng×h/mL, respectively. The geometric mean ratios (90% CI) between the two formulations were 1.1273 (1.0286 – 1.2355) for Cmax, 1.054 (1.0115 – 1.0980) for AUClast, and 1.0395 (0.9959 – 1.0851) for AUC∞. The changes of serum uric acid at 24 hours after reference and test formations were comparable (–1.36 mg/dL for reference and –1.37 mg/dL for test; p = 0.892). Conclusion: The results of the present study indicated that the reference and test formulations have comparable pharmacokinetics and that these two formulations meet the regulatory criteria for bioequivalence. In addition, the reduction of serum UA levels in the reference formulation was similar to that of the test formulation after a single dose.Correspondence to:
Ji-Young Park, MD, PhD
Department of Clinical Pharmacology and Toxicology
Anam Hospital, University College of Medicine
126-1, 5-Ga, Anamdong, Sungbuk-Gu,
Seoul, 136-705 Korea
Email: [email protected]
Original
Pharmacokinetics and safety of 3,4-diaminopyridine base in healthy Japanese volunteers
Natsuko Ishida, Erina Kobayashi, Yuya Kondo, Ryo Matsushita, and Kiyonobu Komai
Price
42.00 $
Page No. 674
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 8/2015 (674-680)
Pharmacokinetics and safety of 3,4-diaminopyridine base in healthy Japanese volunteers
Natsuko Ishida1, Erina Kobayashi2, Yuya Kondo2, Ryo Matsushita2, and Kiyonobu Komai3
1Department of Pharmacy, National Hospital Organization Iou Hospital, 2Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, and 3Department of Neurology, National Hospital Organization Iou Hospital, Ishikawa, Japan
Objective: 3,4-diaminopyridine (3,4-DAP) is commonly used for treating neuromuscular diseases, such as the Lambert-Eaton myasthenic syndrome, but the pharmacokinetics of 3,4-DAP base have not been investigated. We therefore studied 3,4-DAP base pharmacokinetics in healthy Japanese volunteers. Materials and methods: In this crossover study, we administered a single oral dose of 10 or 20 mg 3,4-DAP base to healthy Japanese volunteers (n = 5) after food intake, or 10 mg 3,4-DAP to fasting individuals. We measured serum 3,4-DAP concentrations, performed electrocardiography (ECG), and administered questionnaires. Results: After administration of 10 or 20 mg 3,4-DAP following food intake, the maximum serum concentrations (Cmax) were 8.09 ± 4.47 ng/mL and 35.8 ± 15.7 ng/mL, respectively (mean ± standard deviation; SD), and the areas under the serum concentration-time curve (extrapolated to infinity) were 639 ± 213 ng×min/mL and 2,097 ± 936 ng×min/mL (mean ± SD), respectively. Administration to fasted individuals indicated that food intake did not significantly alter 3,4-DAP pharmacokinetics. ECG showed no clinically significant changes, but PR intervals were prolonged in all cases. Two out of 5 subjects showed perioral paresthesia symptoms after administration of 20 mg 3,4-DAP. Conclusion: This study indicated that 3,4-DAP base pharmacokinetics were non-linear. Although no clinically significant changes in ECG were observed, it is advisable to perform ECG periodically during 3,4-DAP administration in order to monitor cardiac function. Moreover, the development of perioral paresthesia may be dependent on the dose of 3,4-DAP used.Correspondence to:
Natsuko Ishida, MPharm
Department of Pharmacy
National Hospital Organization Iou Hospital
Ni73-1, Iwade-machi, Kanazawa, Ishikawa 920-0192, Japan
Email: [email protected]
Original
Evaluation of the pharmacokinetics and safety of single and multiple ceftaroline fosamil infusions in healthy Chinese and Western subjects
Li Yang, Maria Sunzel, Peng Xu, Timi Edeki, David Wilson, Jianguo Li, and Haiyan Li
Price
42.00 $
Page No. 681
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 8/2015 (681-691)
Evaluation of the pharmacokinetics and safety of single and multiple ceftaroline fosamil infusions in healthy Chinese and Western subjects
Li Yang1, Maria Sunzel2, Peng Xu3, Timi Edeki4, David Wilson5, Jianguo Li6, and Haiyan Li1
1Peking University Third Hospital, Beijing, China, 2Contractor at AstraZeneca, Wilmington, DE, USA, 3Formerly at AstraZeneca China, Shanghai, China, 4AstraZeneca, Wilmington, DE, USA, 5AstraZeneca, Alderley Park, Cheshire, UK, and 6AstraZeneca, Waltham, MA, USA
Objectives: Two phase I studies in healthy Chinese (NCT01458743) and Western (NCT01612507) subjects evaluated the pharmacokinetics (PK) and safety of single and multiple ceftaroline fosamil 600 mg infusions administered every 8 or 12 hours (q8h or q12h). Methods: Each study enrolled subjects sequentially into 1 of 2 cohorts (cohort 1: 60-minute infusions; cohort 2: 120-minute infusions). All subjects in the Chinese (n = 26) study received openlabel ceftaroline fosamil; in the Western study, subjects (n = 41) in each cohort were randomized 3 : 1 to ceftaroline fosamil or placebo infusions. Single infusions were administered on days 1 and 8. On days 2 – 7 (3 – 7 for Chinese study, cohort 1) subjects received q12h or q8h infusions. Plasma and urine were collected on days 1 and 8 for PK analysis. Results: Ceftaroline PK was linear and time-independent following single and multiple doses of ceftaroline fosamil. The magnitude and timing of peak plasma concentrations of ceftaroline (active metabolite), ceftaroline fosamil (prodrug), and ceftaroline M-1 (inactive metabolite) varied according to the ceftaroline fosamil dosing schedule (q12h or q8h) and infusion duration (60 minutes or 120 minutes), but overall plasma ceftaroline exposures within the respective dosing intervals were broadly similar across cohorts. The most frequent adverse events were rash/drug eruption, most of which were of mild-moderate intensity and considered related to treatment. Conclusions: Ceftaroline PK was broadly similar in healthy Chinese and Western subjects receiving equivalent dose regimens. The tolerability profile of ceftaroline fosamil in Chinese and Western subjects was consistent with previous clinical trials.Correspondence to:
Professor Haiyan Li
Peking University Third Hospital
49 Huayan North Road, Haidian, Beijing, China
Email: [email protected]
Case Report
Successful use of infliximab and tacrolimus in a patient with Crohn’s disease
Xavier Cortes, Joaquín Borrás-Blasco, Josefa Rodríguez, Marta Moreno, Jose Ramón Molés and Elvira Castera
Price
42.00 $
Page No. 692
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 8/2015 (692-696)
Successful use of infliximab and tacrolimus in a patient with Crohn’s disease
Xavier Cortes1, Joaquín Borrás-Blasco2, Josefa Rodríguez1, Marta Moreno1, Jose Ramón Molés1, and Elvira Castera2
1Gastroenterology Section, Internal Medicine and 2Pharmacy Service, Hospital de Sagunto, Sagunto, Spain
Objective: To report a case of successful use of infliximab (IFX) and tacrolimus (TAC) in a patient with Crohn’s disease (CD). Case summary: A 42-year-old man with no significant previous medical history was referred to our emergency department because of a 3-month history of weight loss, severe abdominal pain, and bloody diarrhea. His Harvey Bradshaw Index was 39. Ileocolonoscopic revealed severe Crohn colitis. Treatment with IFX 5 mg/kg, azathioprine 2.5 mg/kg/day and corticosteroids was started. After a second IFX infusion, he remained with symptoms with a Harvey Bradshaw Index of 17. An IFX dose intensification of 10 mg/kg every 8 weeks was prescribed. After 16 weeks, a new colonoscopic examination revealed multiple deep ulcerations in sigma and rectum. IFX was intensified to 10 mg/kg every 6 weeks. After 4 doses of IFX intensified dose, the patient’s clinical condition was not improved, with a Harvey Bradshaw Index of 10. Azathioprine (AZA) 2.5 mg/kg/day was suspended. Tacrolimus 0.2 mg/kg/day as a compassionate use was added to IFX 10 mg/kg every 6 weeks. After 6 months of combination therapy, the patient was in clinical remission. His Harvey Bradshaw Index was 3. After 1 year on combination IFX and TAC therapy, the patient continued in clinical remission. Conclusions: This case documents that the combination therapy of IFX and TAC could be selected as an effective approach for patients with CD refractory to IFX dose-intensification plus AZA. However, further studies need to be performed to evaluate the efficacy of this combination therapy.Correspondence to:
Xavier Cortes, MD
Gastroenterology Section
Internal Medicine Hospital de Sagunto (Spain)
Avda Ramon y Cajal s/n Sagunto 46520, Valencia, Spain
Email: [email protected]
Bioavailability Section
Formulation and bioequivalence of two sildenafil 50 mg film-coated tablets after a single oral administration
Abdel Naser Zaid, Rowa’ Al Ramahi, Rana Bustami, and Ayman Mousa
Price
42.00 $
Page No. 697
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 53 – No. 8/2015 (697-704)
Formulation and bioequivalence of two sildenafil 50 mg film-coated tablets after a single oral administration
Abdel Naser Zaid1, Rowa’ Al Ramahi1, Rana Bustami2, and Ayman Mousa3
1Department of Pharmacy, Faculty of Medicine & Health Sciences, An-Najah National University, Nablus, Palestine, 2Pharmaceutical Research Unit, Amman, Jordan, and 3R&D Department Avalon Pharma (Middle East Pharmaceutical Industries Co. Ltd), Riyadh, KSA
Objective: The aims of this study were to establish a bioanalytical method and to evaluate the bioequivalence of two drug products; a generic sildenafil 50 mg filmcoated vs. the brand drug Viagra® 50 mg filmcoated tablets. Method: Bioequivalence of tablets was tested by comparisons against the reference brand product in accordance with the requirements of the Declaration of Helsinki, the current Good Clinical Practice (GCP) Guidelines and the International Conference Harmonization (ICH). Results: The relationship between concentration and peak area ratio was found to be linear within the range of 1.435 – 410.023 ng/mL for sildenafil. The correlation coefficient (r) was always greater than 0.99 during the course of the validation Statistical comparison of the main pharmacokinetic parameters showed no significant difference between test and reference. The 90% CIs of geometric mean ratios (test to reference ratios) were 99.656%, 99.806%, and 109.227% for AUC0–last, AUC0–∞, and Cmax, respectively. These pharmacokinetic parameter values lie within the FDA and European Medicines Agency specified bioequivalence limit (80 – 125%). Both formulations were well tolerated by all subjects and they were discharged in good health. Conclusion: The tested drug product was bioequivalent to the reference drug and had the same safety profile.Correspondence to:
Prof. Abdel Naser Zaid
Head of Department of Pharmacy
Faculty of Medicine & Health Sciences
An-Najah National University, Nablus, P.O.Box 7, Palestine
Email: [email protected]
