Volume 55 (2017), No. 7/2017(July)
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Original Research
Actual use of and adherence to ibuprofen 400 mg tablet dosing instructions in a simulated OTC environment
Suzanne Meeves, Rina Leyva, Clark Richardson, Brenda Wilson, David Savastano
Price
42.00 $
Page No. 547
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (547-557)
Actual use of and adherence to ibuprofen 400 mg tablet dosing instructions in a simulated OTC environment
Suzanne Meeves1, Rina Leyva2, Clark Richardson3, Brenda Wilson4, David Savastano1
1Pfizer Consumer Healthcare, Department of Clinical Research, 2Pfizer Consumer Healthcare, Department of Biostatistics and Analysis, Madison, NJ, 3PEGUS Research, Inc., Project Management, Salt Lake City, UT, and 4Pfizer Consumer Healthcare, Department of Clinical Operations, Madison, NJ, USA
Objective: Evaluate adherence of US consumers to proposed label directions for a new 400 mg ibuprofen formulation. Methods: In this single-arm, open-label, multicenter, 30-day study simulating an over-the-counter (OTC)-like environment, US analgesic consumers reviewed proposed product packaging for a new 400 mg ibuprofen formulation and made a purchase decision. Purchasers used the product as needed and recorded use over 30 days. Outcomes included the percentage of participants who exhibited correct or acceptable product use for the primary endpoint (not exceeding 1,200 mg/day > 2 times during the study) or secondary endpoint (not exceeding 400 mg/dose > 2 times during the study) and adherence to the labeled dosing interval of 6 – 8 hours. Primary endpoint success was met if the lower bound of the 95% confidence interval (CI) was ≥ 85%. Results: Of 685 purchasers providing use data, correct or acceptable use behavior occurred in 95.2% (95% CI: 93.6%, 96.8%) regarding total daily dose and in 84.4% (95% CI: 81.7%, 87.1%) regarding the number of tablets taken per dosing occasion. Most participants (87.3%) never used > 1,200 mg/day or took > 1 tablet/dose (78.1%). Nearly 43% of subjects re-dosed within 6 hours of the previous dose; of these, ~ 82% re-dosed between the 4- and 6-hour time intervals. Adverse events were consistent with prior ibuprofen 200 mg experience. Conclusion: This study provides evidence that a majority of US consumers would be able to use OTC ibuprofen 400 mg tablets in a manner consistent with product labeling. Misuse rates were low and unlikely to generate an excess risk of clinically important adverse events.
Correspondence to:
Suzanne Meeves, PharmD, MBA,
Director
Clinical Research, Pfizer Consumer Healthcare
1 Giralda Farms, Madison, NJ 07940, USA
Email: [email protected]
Original Research
Population pharmacokinetics of vancomycin in Chinese infants
Xiao-yan Sheng, Chao-yang Chen, Ling-yue Ma, Ya-ou Liu, Ying Zhou, and Yi-min Cui
Price
42.00 $
Page No. 558
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (558-566)
Population pharmacokinetics of vancomycin in Chinese infants
Xiao-yan Sheng, Chao-yang Chen, Ling-yue Ma, Ya-ou Liu, Ying Zhou, and Yi-min Cui
Department of Pharmacy, Peking University First Hospital, Beijing, China
Objective: To determine the pharmacokinetics (PK) of vancomycin in Chinese infant patients using a population pharmacokinetic (PKK) approach in order to provide support for individualized vancomycin therapy. Method: The data included 72 sets of steady-state peak and trough serum concentrations from 61 infants (0 – 1 years). PPK analysis was performed using the nonlinear mixed-effects modeling software. Inter- and intraindividual variability was estimated for the clearance and distribution volume of vancomycin. The potential effects of patient sex, postnatal age, postconceptional age, height, weight, body surface area, body mass index, alanine aminotransferase, aspartate aminotransferase, total protein, albumin, white blood cell count, serum creatinine, and concomitant medications on vancomycin PKs were explored. Results: A one-compartment linear model with first-order elimination was used to describe the data. Weight and postnatal age had a significant influence on vancomycin clearance. The typical population parameter estimates of clearance and distribution volume were 0.46 L/h and 4.45 L, respectively. Goodness-of-fit plots and bootstrap outcomes confirmed the relatively good stability and prediction capability of the model. Conclusion: This study initially established a vancomycin PPK model to estimate individual PK parameters in Chinese infant patients.
Correspondence to:
Prof. Yi-min Cui,
Department of Pharmacy, Peking University, First Hospital
No.6, Da Hong Luo Chang Street, Beijing,100034, China
Email: [email protected]
Original Research
Plasma and saliva concentrations of abacavir, tenofovir, darunavir, and raltegravir in HIV-1-infected patients
Eiko Yamada, Ritsuo Takagi, Yoshinari Tanabe, Hiroshi Fujiwara, Naoki Hasegawa, Shingo Kato
Price
42.00 $
Page No. 567
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (567-570)
Plasma and saliva concentrations of abacavir, tenofovir, darunavir, and raltegravir in HIV-1-infected patients
Eiko Yamada1, Ritsuo Takagi1, Yoshinari Tanabe2, Hiroshi Fujiwara3, Naoki Hasegawa3, Shingo Kato4
1Division of Oral and Maxillofacial Surgery, 2Division of Infection Control and Prevention, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 3Center for Infectious Diseases and Infection Control, and 4Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan
Objective: We studied the relationships between plasma and saliva concentrations of antiretroviral drugs to explore whether saliva can be used for therapeutic drug monitoring (TDM). Methods: Abacavir (ABC), tenofovir (TFV), darunavir (DRV), and raltegravir (RAL) in plasma and saliva from 30 HIV-1-infected patients were quantified using liquid chromatography-tandem mass spectrometry. Results: Mean saliva-to-plasma concentration ratios were 0.623 (ABC), 0.024 (TFV), 0.065 (DRV), and 0.0135 (RAL), which agree with the plasma protein binding rates except TFV. Significant correlations were evident between saliva and plasma concentrations of ABC, DRV, and RAL. Conclusions: This study suggests that plasma concentrations of ABC, DRV, and RAL can be estimated from their saliva concentrations and that the saliva concentration of some antiretroviral drugs reflects the unbound drug concentration in plasma.
Correspondence to:
Shingo Kato, PhD,
Department of Microbiology and Immunology
Keio University School of Medicine
35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Email: [email protected]
Original Research
A review of six methods for monitoring infliximab concentrations and antibodies to infliximab
Fang Cao, Hailong Cao, and Xiaocang Cao
Price
42.00 $
Page No. 571
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (571-580)
A review of six methods for monitoring infliximab concentrations and antibodies to infliximab
Fang Cao, Hailong Cao, and Xiaocang Cao
Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China
Anti-TNF-α therapy, such as infliximab (IFX), has profoundly changed treatment to induce and maintain remission for inflammatory bowel diseases patients who do not respond to conventional therapies. Unfortunately, IFX, as a chimeric protein, is potentially immunogenic, and antibodies to infliximab (ATI) may interfere with the pharmacodynamics and pharmacokinetics of the drug, thus resulting in a loss of response for a substantial proportion of patients. The clinical efficacy of IFX is correlated with the levels of IFX and ATI. Therefore, monitoring patients for the trough levels of IFX and the presence of ATI is very important. The procedures and characteristics of six assays for monitoring IFX and ATI are described in this review, and the comparisons between them are also discussed. To date, there has been no optimal assay for monitoring IFX and ATI. Therefore, many technical problems need to be solved to make therapeutic drug and immunogenicity monitoring a part of routine clinical management.
Correspondence to:
Xiaocang Cao, PhD
Department of Gastroenterology and Hepatology
Tianjin Medical University General Hospital
154 AnShan Street, Heping District, Tianjin, China
Email:
[email protected]
Original Research
Trends in the prescribing of atypical antipsychotics in elderly patients with dementia in Korea
Namjoo Seo, Inmyung Song, Hyekyung Park, Dongmun Ha, Ju-Young Shin
Price
42.00 $
Page No. 581
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (581-587)
Trends in the prescribing of atypical antipsychotics in elderly patients with dementia in Korea
Namjoo Seo*, Inmyung Song*, Hyekyung Park, Dongmun Ha, Ju-Young Shin
School of Pharmacy, Sungkyunkwan University, Suwon, Korea
Objective: In 2005, the Food and Drug Administration warned that atypical antipsychotics (AAPs) increased mortality in elderly patients with dementia. We investigated AAP prescribing in elderly patients with dementia in the ambulatory setting in Korea and the factors affecting AAP prescribing in elderly patients with dementia. Methods: Subjects ≥ 65 years of age with at least one diagnosis of dementia (ICD-10: F00-F03, G30, G31.8) from January 1 to December 31, 2013 were identified from a health insurance database. Using multiple logistic regression analysis to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for AAP prescribing in elderly patients with dementia, AAP user prevalence was estimated and presented by dementia type, individual AAP, medical institution, and region. Results: A total of 61,550 elderly patients with dementia were identified: 6,504 (9.8%) received AAPs, 12.3% of them had Alzheimer’s disease; only 2 patients with vascular dementia were prescribed AAPs (0.04%). Female patients were less likely to be prescribed AAPs than male patients. The likelihood of AAP prescribing was higher for patients aged 70 years and older than for those < 70 years. AAP prescribing was higher for patients visiting secondary care institutions (OR, 1.12; 95% CI, 1.65 – 1.74) than for those visiting primary care institutions, and for patients in cities (OR, 1.57; 95% CI, 1.52 – 1.62) than for those in metropolitan regions. Conclusions: Although the prevalence of AAP prescribing has decreased, especially among patients with vascular dementia, it remains high. Efforts to reduce AAP use should focus on secondary care institutions in nonmetropolitan regions.
*Co first authorsCorrespondence to:
Ju-Young Shin, PhD, School of Pharmacy, Sungkyunkwan University 2066 Seobu-ro, Jangan-gu, Suwon, Gyeong gi-do, South Korea
Email: [email protected]
Original Research
Comparison of the efficacies of three empirically-selected antibiotics for treating Acinetobacter baumannii pulmonary infection: experience from a teaching hospital in China
Ping Li, Xiaobo Wang, Weixia Wang, Xiaojing Zhao
Price
42.00 $
Page No. 588
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (588-593)
Comparison of the efficacies of three empirically-selected antibiotics for treating Acinetobacter baumannii pulmonary infection: experience from a teaching hospital in China
a
Ping Li, Xiaobo Wang, Weixia Wang, Xiaojing Zhao
Emergency Intensive Care Unit, the Second Affiliated Hospital of Xian Jiaotong University, Xi’an, China
Objective: Infections due to multidrug- and extensively drug-resistant forms of Acinetobacter baumannii (MDR-AB and XDR-AB, respectively) have become increasingly prevalent. This retrospective study compared the outcomes of patients infected with MDR-AB or XDR-AB and treated with one of three antibiotics. Methods: Enrolled were patients with MDR-AB or XDR-AB pulmonary infection based on their first sputum culture. Patients were treated empirically with carbapenems (n = 46), tigecycline (n = 25), or cefoperazone/sulbactam (cefina-SB; n = 35). The therapeutic efficacies of the drugs and patient outcomes were retrospectively compared. Bacterial resistance to the three antibacterials was determined based on sputum cultures from all enrolled patients. Results: The study included 106 patients. After 7 days of treatment, the favorable response rates to tigecycline (60%) and to cefina-SB (71.4%) were statistically similar (p = 0.355) but significantly higher than that to carbapenems (23.9%; p = 0.003 and p < 0.001, respectively). Sputum culture analyses to determine antibiotic susceptibility indicated that 10.4% of patients’ sputum cultures were susceptible to carbapenems, 76.4% to tigecycline, and 66.0% to cefina-SB. In addition, 58.5% were susceptible to both tigecycline and cefina-SB. Conclusions: Tigecycline and cefina-SB appeared to be more effective against MDR-AB and XDR-AB pulmonary infections than carbapenems, especially for patients who had been admitted to the intensive care unit multiple times.
Correspondence to:
Xiaojing Zhao, PhD, MD
Emergency Intensive Care Unit
The Second Affiliated Hospital of Xi’an Jiaotong University
Xi’an, 710004, China
Email: [email protected]
Original Research
Safety of azathioprine and 6-mercaptopurine in patients with inflammatory bowel disease naïve to thiopurine treatment
Ram Alaish, David Lundgren, Ole B. Suhr, Mårten Werner, and Pontus Karling
Price
42.00 $
Page No. 594
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (594-600)
Safety of azathioprine and 6-mercaptopurine in patients with inflammatory bowel disease naïve to thiopurine treatment
Ram Alaish, David Lundgren, Ole B. Suhr, Mårten Werner, and Pontus Karling
Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden
Objectives: To determine if 6-mercaptopurine (MP) is better tolerated than azathioprine (AZA) as the initial thiopurine treatment in patients suffering from inflammatory bowel disease (IBD). Switching patients with IBD from AZA to MP is advocated in patients intolerant to AZA. However, no study has determined if MP is more suited than AZA as a first-line treatment for patients who are naïve to thiopurine treatment. Study: The tolerance of AZA and MP treatments in clinical practice was retrospectively evaluated from start to 12 months after initiating treatment in 113 patients with IBD who were all naïve to thiopurines (82 patients treated with AZA and 31 patients with MP). Results: 65% of the patients treated with AZA and 61% of the patients treated with MP tolerated their treatment during 12 months (i.e., no group difference, p = 0.742). No difference in reported side effects between the two treatments was observed. The mean equivalent initial dose (0.92 vs. 0.61 mg/kg; p < 0.001) and the mean equivalent dose at 12 months (1.98 vs. 1.65 mg/kg; p = 0.014) was significantly higher in the MP group vs. the AZA group. The proportion of patients with ΔMCV ≥ 7 at 12 months was numerically higher in the MP group than in the AZA group (53% vs. 31%; p = 0.090). Conclusions: In this retrospective observational study, no differences in tolerance or adherence between AZA and MP were observed in patients naïve to thiopurines. However, MP treatment was at a higher equivalent thiopurine dose than AZA treatment, which tended to be associated with better treatment response.
Correspondence to:
Pontus Karling, PhD
Department of Medicine/Gastroenterology
University hospital of Umeå
90185 Umeå, Sweden
Email: [email protected]
Original Research
Parecoxib sodium pretreatment reduces myoclonus after etomidate: A prospective, double-blind, randomized clinical trial
Xiuze Li, Jun Liu, Mengjun Zhou, Chaojing Zhou
Price
42.00 $
Page No. 601
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (601-605)
Parecoxib sodium pretreatment reduces myoclonus after etomidate: A prospective, double-blind, randomized clinical trial
Xiuze Li1, Jun Liu2, Mengjun Zhou3, Chaojing Zhou1
1Department of Anesthesiology, 2Department of General Surgery, and 3Department of Health Statistics, Mianyang Central Hospital, Sichuan, China
Objective: Myoclonus induced by etomidate during induction of general anesthesia is a common phenomenon. This prospective, randomized, saline-controlled clinical study was performed to evaluate the effect of parecoxib sodium pretreatment on the incidence and severity of etomidate-induced myoclonus. Methods: 60 patients, American Society of Anesthesiologists (ASA) physical status I or II, aged 20 to 60 years, who were scheduled to undergo elective laparoscopic cholecystectomy under general anesthesia, were allocated randomly into one of two groups to receive parecoxib sodium 40 mg intravenous (group P, n = 30) or the same volume of saline (group S, n = 30) 30 minutes before administration of etomidate (0.3 mg/kg). Myoclonus was assessed on a scale of 0 – 3. Postoperative side effects were recorded. Results: The two groups were comparable with regard to baseline characteristics. The incidence of myoclonus was significantly lower in the parecoxib sodium group (11/30; 37%) than in the saline group (21/30; 70%) (p < 0.05). The severity of myoclonic movements was also significantly reduced by parecoxib sodium (p < 0.05). There were no significant differences between the two groups with respect to postoperative side effects. Conclusions: Pretreatment with intravenous injection of parecoxib sodium 40 mg significantly reduced the incidence and severity of etomidate-induced myoclonus without significant side effects.
Correspondence to:
Dr. Xiuze Li
Department of Anesthesiology
Mianyang Central Hospital
12 Changjia Lane, Mianyang, Sichuan 621000, China
Email: [email protected]
Original Research
Tralokinumab pharmacokinetics and tolerability when administered by different subcutaneous injection methods and rates
Meena Jain, Diane Doughty, Corbin Clawson, Xiaobai Li, Nicholas White, Balaji Agoram, René van der Merwe
Page No. 606
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (606-618)
Tralokinumab pharmacokinetics and tolerability when administered by different subcutaneous injection methods and rates
Meena Jain1, Diane Doughty2, Corbin Clawson2, Xiaobai Li3, Nicholas White4, Balaji Agoram5, René van der Merwe1
1Clinical Development, MedImmune, Cambridge, UK, 2Drug Delivery and Device Development, 3Clinical Biostatistics, MedImmune, Gaithersburg, MD, USA,
4Clinical Pharmacology, Drug Metabolism and Pharmacokinetics, MedImmune, Cambridge, UK, and 5Clinical Pharmacology, Drug Metabolism and Pharmacokinetics, MedImmune, Mountain View, CA, USA
Objective: Tralokinumab, administered as two 1-mL subcutaneous injections every 2 weeks, at the target dose 300 mg, has been shown to improve lung function in patients with asthma. This study evaluated the pharmacokinetic (PK) and tolerability profile of tralokinumab 300 mg when administered by different rates of subcutaneous injection, as part of a pilot investigation of new injection regimens. Methods: This phase I study randomized 60 healthy adults to receive 300 mg tralokinumab, as two 1-mL subcutaneous injections, each delivered over 10 seconds, or one 2-mL injection delivered over 10 seconds (12 mL/min), 1 minute (2 mL/min), or 12 minutes (0.167 mL/min). Results: No differences in the PK profile of tralokinumab were observed between cohorts. Immediately following injection, injection-site pain intensity (mean (SD)) was lowest following 0.167 mL/min injection (5.1 mm (8.0) via visual analog scale (VAS)) and greatest following 12 mL/min injection (41 mm (27.7) via VAS); with mean injection-site pruritus intensity low for all participants. Two types of local injection-site reactions were observed: erythema (58.3%) and hematoma/bleeding (18.3%). All treatment-emergent adverse events were mild. Conclusions: Tralokinumab 300 mg is well tolerated, with comparable PK, when administered by a single 2-mL injection at different rates of subcutaneous injection vs. two 1-mL injections.
Correspondence to:
Dr. Meena Jain, PhD
Clinical Development, MedImmune
Granta Park,
Cambridge,
CB21 6GH, UK
Email: jainm@
MedImmune.com
Original Research
Vascular permeability determined using multi-slice spiral CT perfusion can predict response to chemoradiotherapy in patients with advanced cervical squamous cell carcinoma
Jie Liu, Hua Fan, Guang-Ping Qiu
Price
42.00 $
Page No. 619
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (619-626)
Vascular permeability determined using multi-slice spiral CT perfusion can predict response to chemoradiotherapy in patients with advanced cervical squamous cell carcinoma
Jie Liu, Hua Fan, Guang-Ping Qiu
Department of Interventional, NingBo No.2 Hospital, NingBo, China
Aim: This study aims to use multi-slice spiral computed tomography (CT) perfusion to investigate the predictive value of vascular permeability in determining the response of patients with advanced cervical squamous-cell carcinoma (CSCC) to chemoradiotherapy treatment. Methods: 196 patients with advanced CSCC were recruited. Multi-slice spiral CT perfusion was performed before chemoradiotherapy, and perfusion parameters, such as blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface (PS), were obtained. After treatment, patients were divided into a sensitive group and a resistant group. Receiver operating characteristic (ROC) analysis was performed to evaluate the predictive value of the perfusion parameters. The association of the perfusion parameters with the response of CSCC to chemoradiotherapy was analyzed using logistic regression analysis. Results: Lesion size and treatment duration were remarkably different between the sensitive (n = 101) and resistant groups (n = 95) (both p < 0.05). Before chemoradiotherapy, the sensitive group had a significantly higher BV and PS than the resistant group (both p < 0.05). The logistic regression analysis showed that lesion size, BV, and PS are associated with the response of CSCC to chemoradiotherapy (all p < 0.05). The sensitivity and the specificity of BV and PS were 65.3% and 83.2% and 75.2% and 72.6%, respectively. Conclusion: BV and PS values determined using CT perfusion correlate with and predict the response to chemoradiotherapy in the treatment of advanced CSCC. Patients with smaller lesions require shorter periods of treatment.
Correspondence to:
Dr. Guang-Ping Qiu
Department of Interventional, NingBo No.2 Hospital
No.41 Northwest Road, Haishu District
NingBo 315010, Zhejiang Province, P.R. China
Email: [email protected]
Case
Report
Recurrent trimethoprim-sulfamethoxazole-induced aseptic meningitis with associated ampicillin-induced myoclonic twitches
Anna Fisse, Katrin Straßburger-Krogias, Ralf Gold, Gisa Ellrichmann
Price
42.00 $
Page No. 627
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (627-629)
Recurrent trimethoprim-sulfamethoxazole-induced aseptic meningitis with associated ampicillin-induced myoclonic twitches
Anna Fisse
, Katrin Straßburger-Krogias, Ralf Gold, Gisa Ellrichmann
Department of Neurology, Ruhr University Bochum, St. Josef-Hospital, Bochum, Germany
Objective: To report a case of recurrent trimethoprim-sulfamethoxazole-induced aseptic meningitis with associated ampicillin-induced myoclonic twitches. Materials and methods: The patient was investigated using cerebral computed tomography, magnetic resonance imaging, cerebrospinal fluid examination, and electroencephalography. Written informed consent was obtained from the patient for access to clinical files for research purposes and publication. Results: We present a middle-aged woman with two recurrent episodes of aseptic meningitis after treatment with trimethoprim-sulfamethoxazole. Additionally, she developed myoclonic twitches as a rare side effect of ampicillin. Conclusion: Aseptic meningitis is a rare adverse reaction to medications like antibiotics. The pathogenesis of trimethoprim-sulfamethoxazole-induced aseptic meningitis is not yet completely understood, but an immune-mediated hypersensitivity reaction is suspected. If patients with an antibiotic therapy due to a systemic or local infection present with severe headache, not only common diagnosis of a parainfectious headache, but also antibiotic-induced aseptic meningitis should be considered.
Correspondence to:
Anna Lena Fisse, MD
Department of
Neurology, Ruhr University Bochum
St. Josef-Hospital
Gudrunstrasse 56, 44791 Bochum, Germany
Email: [email protected]
Case
Report
Mirtazapine-induced steatosis
Elin Thomas, Hasan Haboubi, Namor Williams, Aled Lloyd, and Chin Lye Ch’ng
Price
42.00 $
Page No. 630
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (630-632)
Mirtazapine-induced steatosis
Elin Thomas, Hasan Haboubi, Namor Williams, Aled Lloyd, and Chin Lye Ch’ng
Department of Gastroenterology, Singleton Hospital, Swansea, UK
Mirtazapine is a commonly used drug indicated for the treatment of severe depression. It works as a presynaptic α2-adrenoreceptor antagonist that increases central noradrenergic and serotonergic neurotransmission, and it is metabolized by the p450 cytochrome oxidase system. There is evidence within the literature to suggest a link between antidepressants and increased liver enzymes, although case reports demonstrating a link between mirtazapine specifically and steatosis are sparse. Here, we present a case of mirtazapine-induced steatosis in a 48-year-old office worker. She presented with painless jaundice of 2 days duration and generalized lethargy and peripheral edema present for 3 weeks beforehand. Extensive investigations were undertaken to identify the cause of her jaundice but no biochemical, blood-borne, or anatomical cause could be found. Mirtazapine was subsequently stopped, and her liver function, both clinically and biochemically, improved rapidly. She made a full recovery after discontinuation of her mirtazapine.
Correspondence to:
Dr. Chin Lye Ch’ng
Department of Gastroenterology, Singleton Hospital
Sketty Lane, Swansea, SA2 8QA UK
Email: chinlye.ch’ng@
wales.nhs.uk
Bioavailability Section
Presentation of coefficient of variation for bioequivalence sample-size calculation
Yi Lin Lee, Wen Yao Mak, Irene Looi, Jia Woei Wong, Kah Hay Yuen
Price
42.00 $
Page No. 633
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 7/2017 (633-638)
Presentation of coefficient of variation for bioequivalence sample-size calculation
Yi Lin Lee1*, Wen Yao Mak1*, Irene Looi1, Jia Woei Wong2, Kah Hay Yuen2
1Clinical Research Centre, Hospital Seberang Jaya, Jalan Tun Hussein Onn, and 2Attest Research Sdn Bhd, BA/BE Laboratory, Kompleks EUREKA, Universiti Sains Malaysia, Pulau Pinang, Malaysia
The current study aimed to further contribute information on intrasubject coefficient of variation (CV) from 43 bioequivalence studies conducted by our center. Consistent with Yuen et al. (2001), current work also attempted to evaluate the effect of different parameters (AUC0–t, AUC0–∞, and Cmax) used in the estimation of the study power. Furthermore, we have estimated the number of subjects required for each study by looking at the values of intrasubject CV of AUC0–∞ and have also taken into consideration the minimum sample-size requirement set by the US FDA. A total of 37 immediate-release and 6 extended-release formulations from 28 different active pharmaceutical ingredients (APIs) were evaluated. Out of the total number of studies conducted, 10 studies did not achieve satisfactory statistical power on two or more parameters; 4 studies consistently scored poorly across all three parameters. In general, intrasubject CV values calculated from Cmax were more variable compared to either AUC0–t and AUC0–∞. 20 out of 43 studies did not achieve more than 80% power when the value was calculated from Cmax value, compared to only 11 (AUC0–∞) and 8 (AUC0–t) studies. This finding is consistent with Steinijans et al. (1995) [2] and Yuen et al. (2001) [3]. In conclusion, the CV values obtained from AUC0–t and AUC0–∞ were similar, while those derived from Cmax were consistently more variable. Hence, CV derived from AUC instead of Cmax should be used in sample-size calculation to achieve a sufficient, yet practical, test power.
*Contributed equallyCorrespondence to:
Yi Lin Lee, RPh
Clinical Research Centre, Hospital Seberang Jaya
Jalan Tun Hussein Onn
13700 Seberang Jaya, Pulau Pinang, Malaysia
Email:
[email protected]
