Volume 55 (2017), No. 5/2017(May)
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Review
Generic antiretrovirals for the treatment of HIV: a novel challenge for Western countries?
Dario Cattaneo, Massimo Andreoni, Gianpiero Carosi, Roberto Cauda, Adriano Lazzarin, Giuliano Rizzardini
Price
42.00 $
Page No. 381
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 5/2017 (381-393)
Generic antiretrovirals for the treatment of HIV: a novel challenge for Western countries?
Dario Cattaneo1, Massimo Andreoni2, Gianpiero Carosi3, Roberto Cauda4, Adriano Lazzarin5, Giuliano Rizzardini6,7
1Unit of Clinical Pharmacology, ASST Fatebenefratelli Sacco Hospital, Milan, 2Clinical Infectious Diseases, Tor Vergata University, Rome, 3University of Brescia, Brescia, 4Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, 5Vita-Salute, San Raffaele University, 6Department of Infectious Diseases, ASST Fatebenefratelli Sacco Hospital, Milan, Italy, and 7School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa
The introduction of generic antiretroviral medications in developing countries has resulted in significant CD4 cell restoration, HIV viral decline, and a noteworthy reduction in the time to initiation of therapy. Projection models have also predicted significant cost saving associated with the extensive diffusion of generic antiretrovirals in developed countries. However, some uncertainties on generics have recently been raised. These concerns mainly relate to the adequacy of the study design for bioequivalence testing, the potential for uncontrolled switching from one generic to another, and the loss of adherence if patients switched from fixed-dose coformulations to single components in order to incorporate the new generic drugs. In the present review, we deal with current evidence and potential controversial issues regarding generic antiretrovirals and their underlying economic implications and provide some proposals on how to favor the widespread diffusion of generics in HIV medicine. This may be particularly relevant considering that the safe, systematic switch from patented to generic antiretrovirals could potentially guarantee access to therapies for HIV-infected patients worldwide and lead to money savings that would compensate the expenditure increase resulting from new, innovative HIV drugs.
Correspondence to:
Dario Cattaneo, PharmD, PhD
Unit of Clinical
Pharmacology
ASST Fatebenefratelli Sacco University Hospital
Via Grassi 74, 20157 Milan, Italy
Email: [email protected]
Original Research
Prevalence of bisphosphonate therapy in women with breast cancer treated with aromatase inhibitors in Germany
Louis Jacob, Karel Kostev, Peyman Hadji
Price
42.00 $
Page No. 394
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 5/2017 (394-396)
Prevalence of bisphosphonate therapy in women with breast cancer treated with aromatase inhibitors in Germany
Louis Jacob1, Karel Kostev2, Peyman Hadji3
1Faculty of Medicine, University of Paris 5, Paris, France, 2Department of Epidemiology, IMS Health, Frankfurt, and 3Department of Bone Oncology, Endocrinology and Reproductive Medicine, Nordwest Hospital, Frankfurt, Germany
Purpose: The aim of this study is to analyze the prevalence of bisphosphonate therapy in women with breast cancer (BC) treated with aromatase inhibitors (AI) in Germany. Methods: We included women with BC who started AI therapy between January 2005 and December 2014 (index date) and were followed for a maximum of 24 months. The number of women who received at least one prescription of bisphosphonate during AI therapy was calculated. Results: A total of 6,959 women with BC who received AI therapy between 2005 and 2014 were analyzed. Of these, only 202 (2.9%) received bisphosphonates. Conclusions: The prevalence of bisphosphonate use was low in women with BC treated with AI.
Correspondence to:
Prof. Dr. rer. med.
Karel Kostev
Epidemiology, IMS Health
Darmstädter Landstraße 108
60598 Frankfurt am Main, Germany
Email: kkostev@
de.imshealth.com
Original Research
Continuous infusion of a large dose of CF (folinic acid) and 5-FU combined with CDDP in the treatment of advanced esophageal cancer
Zheng-qiu Zhu, Zu-an Zhu, and Hong-xing Cai
Price
42.00 $
Page No. 397
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 5/2017 (397-402)
Continuous infusion of a large dose of CF (folinic acid) and 5-FU combined with CDDP in the treatment of advanced esophageal cancer
Zheng-qiu Zhu1, Zu-an Zhu2, and Hong-xing Cai3
1Oncology Department, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province, 2Gastroenterology Department, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province, and 3Department of Forensic Medicine, Xuzhou Medical College, Xuzhou, Jiangsu Province, PR China
5-fluorouracil (5-FU) and cisplatin (CDDP) are common chemotherapy drugs used in the treatment of patients with advanced esophageal cancer. We investigated the efficacy of adding a continuous infusion of a large dose of a common adjuvant, citrovorumfactor (CF), to the traditional 5-FU/wCDDP regimen. 50 patients with advanced esophageal cancer were treated with a continuous infusion of CF, 5-FU, and CDDP, and the short-term effects, adverse reactions, and survival periods after treatment were analyzed. Overall, the treatment was effective in 58% of patients, and the therapeutic effects of the first-line of chemotherapy were significantly better than the second-line (u = 4.121, p < 0.05). Patients experienced severe nausea and vomiting in 18.7% of the treatment cycles and experienced severe hair loss or leucopenia in 1.9% of the treatment cycles. The majority of the treatment cycles produced only mild side effects. The median survival period following chemotherapy treatment was 10.6 months (95% confidence interval was 8.146 ~ 13.054 months), with the median survival time of patients with a Karnofsky Performance Status (KPS) score ≥ 80 being significantly longer than that of patients with KPS scores < 80 (χ2 = 41.595, p < 0.05). The median survival time of patients with metastasis to the lymph nodes and surrounding tissue was significantly longer than that of patients with visceral metastasis (χ2 = 32.246, p < 0.05). Cox regression analysis showed that KPS scores before the treatment < 80 (relative risk (RR= = 1.635) and the incidence of visceral metastasis (RR = 1.875) were associated with survival time (p < 0.05). These results suggest that the continuous infusion of a large dose of CF, 5-FU, and CDDP as chemotherapy treatment of advanced esophageal cancer can produce promising short-term results and decrease adverse reactions.Correspondence to:
Professor Hong-xing Cai, Department of Forensic Medicine, Xuzhou Medical College, No. 209, Tongshan Road, Xuzhou 221002, Jiangsu Province, PR, China
Email: [email protected]
Original Research
Regional differences in insulin therapy regimens in five European countries
Wolfgang Rathmann, Marcin Czech, Edward Franek, Karel Kostev
Price
42.00 $
Page No. 403
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 5/2017 (403-408)
Regional differences in insulin therapy regimens in five European countries
Wolfgang Rathmann1, Marcin Czech2, Edward Franek3, Karel Kostev4
1Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany, 2Real World Evidence, IMS Health, 3Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland, and 4Epidemiology, IMS Health, Frankfurt am Main, Germany
Aims: The purpose of this study was to investigate differences of insulin therapy regimens in five European countries. Methods: Proportions of basal bolus therapy (intensified insulin therapy (ICT), basal insulin supported oral therapy (BOT), conventional therapy (CT), and short-acting prandial insulin (SIT) among insulin-treated diabetes patients in Germany (n = 64,055), the UK (n = 6,740), and France (n = 4,779) were estimated using representative general medicine practice databases (Disease Analyzer: 2014). Insulin regimens in Hungary (n = 40,769) and Poland (n = 68,136) were analyzed based on nationwide prescription databases (LRx: 2014). Results: ICT was the most frequent insulin regimen (46 – 81%) in all countries except France (BOT > ICT). SIT showed the lowest use, ranging from 2.5% in the UK to 11.2% in Germany. BOT was more frequently used than CT in Germany and Hungary, which was just the opposite in the UK and Poland. The share of insulin analogs among all prescriptions was higher in Germany, the UK, and France (short-acting insulins: 59 – 98%; basal insulins: 70 – 93%) than in Hungary and Poland (short-acting insulins: 41 – 57%; basal insulins: 23 – 46%) (all p < 0.001). Conclusions: Despite national and international guidelines, insulin regimens differ substantially between European countries. Our results most likely reflect differences in regulations and reimbursement systems, national diabetes care systems as well as patient characteristics and expectations.
Correspondence to:
Prof. Dr. Karel Kostev
QuintilesIMS, Epidemiology,
Darmstädter Landstr. 108
60598 Frankfurt am Main, Germany
Email: [email protected]
Original Research
Association between ABCG2 and SLCO1B1 polymorphisms and adverse drug reactions to regorafenib: a preliminary study
Akimitsu Maeda, Hitoshi Ando, Takashi Ura, Azusa Komori, Ayako Hasegawa, Hiroya Taniguchi, Shigenori Kadowaki, Kei Muro, Masahiro Tajika, Makiko Kobara, Masahide Matsuzaki, Naoya Hashimoto, Mieko Maeda, Yasushi Kojima, Masahiro Aoki, Eisaku Kondo, Akiyoshi Mizutani, and Akio Fujimura
Price
42.00 $
Page No. 409
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 5/2017 (409-415)
Association between ABCG2 and SLCO1B1 polymorphisms and adverse drug reactions to regorafenib: a preliminary study
Akimitsu Maeda1,2, Hitoshi Ando2, Takashi Ura3, Azusa Komori3, Ayako Hasegawa1, Hiroya Taniguchi3, Shigenori Kadowaki3, Kei Muro3, Masahiro Tajika4, Makiko Kobara5, Masahide Matsuzaki1, Naoya Hashimoto1, Mieko Maeda1, Yasushi Kojima6, Masahiro Aoki6, Eisaku Kondo7, Akiyoshi Mizutani1, and Akio Fujimura2
1Department of Pharmacy, Aichi Cancer Center Hospital, Nagoya, 2Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi, 3Department of Clinical Oncology, 4Department of Endoscopy, 5Division of Nursing, Aichi Cancer Center Hospital, 6Division of Molecular Pathology, Aichi Cancer Center Research Institute, Nagoya, and 7Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Objective: Due to the occurrence of severe adverse drug reactions to regorafenib, a drug used in cancer therapy, the identification of a predictive marker(s) is needed to increase the therapeutic applicability of this compound. We therefore investigated whether polymorphisms in the ABCG2 and SLCO1B genes are associated with adverse drug reactions to regorafenib. Methods: For these analyses, 37 Japanese cancer patients were treated with regorafenib, genotyped for polymorphisms in ABCG2 and SLCO1B, and evaluated for drug-related adverse drug reactions. Results: There was no association between the ABCG2 421C>A variant and adverse drug reactions to regorafenib. After treatment, the incidences of increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as increased total bilirubin (grade ≥ 2) were 8%, 4%, and 12%, and 42%, 25%, and 25% among SLCO1B1*1b carriers and non-carriers, respectively. There were no significant associations between elevated ALT and bilirubin and the SLCO1B1*1b allele. However, there were significantly lower incidences of increased AST (8% vs. 42%) and anemia (16% vs. 50%) in SLCO1B1*1b carriers than in non-carriers. Conclusions: The absence of SLCO1B1*1b allele appears to be associated with the development of adverse drug reactions to regorafenib; however, further studies involving larger test groups and other populations are needed to confirm these findings.
Correspondence to:
Akimitsu Maeda, PhD
Department of Pharmacy
Aichi Cancer Center Hospital
1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan
Email: [email protected]
Original Research
Population pharmacokinetics of ticagrelor and AR-C124910XX in patients with prior myocardial infarction
Daniel Röshammar, Martin Bergstrand, Tomas Andersson, Robert F. Storey, Bengt Hamrén
Price
42.00 $
Page No. 416
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 5/2017 (416-424)
Population pharmacokinetics of ticagrelor and AR-C124910XX in patients with prior myocardial infarction
Daniel Röshammar1, Martin Bergstrand2, Tomas Andersson1, Robert F. Storey3, Bengt Hamrén1
1AstraZeneca R&D, Gothenburg, 2Pharmetheus, Uppsala, Sweden, and
3University of Sheffield, Sheffield, UK
Objective: The population pharmacokinetics of ticagrelor and its active metabolite AR-C124910XX were characterized following ticagrelor 60 mg or 90 mg twice daily oral long-term treatment in 4,426 patients with a history of myocardial infarction. Methods: The ticagrelor and AR-C124910XX plasma concentration-time data were described by one-compartment models with first-order absorption or metabolite formation and elimination. Results: Systemic exposure to ticagrelor and AR-C124910XX were stable over time. Ticagrelor apparent clearance (CL/F) was 17 L/h for the 60-mg and 15.4 L/h for the 90-mg dose. The CL/F of AR-C124910XX was 11.1 L/h for the 60-mg and 9.95 L/h for the 90-mg dose. Both ticagrelor and AR-C124910XX CL/F were independently influenced by body weight, sex, age, smoking, and Japanese ethnicity. Female sex and age > 75 years were the only categorical covariates, having more than 20% effect on AR-C124910XX CL/F. Ticagrelor CL/F was 6% higher and 11% lower, whereas AR-C124910XX CL/F was 26% higher and 34% lower for patients weighing 110 and 50 kg, respectively, compared with an 83 kg patient. Conclusions: The small differences in exposure to both ticagrelor and AR-C124910XX between demographic subgroups were in accordance with the consistent efficacy and safety outcomes observed across the population. The results were similar to those observed previously in patients with acute coronary syndromes.
Correspondence to:
Bengt Hamrén, PhD
, AstraZeneca R&D, Gothenburg, Pepparedsleden 1, SE 431 83 Mölndal, Sweden
Email: [email protected]
Original Research
Evaluation of drug-prescribing patterns based on the WHO prescribing indicators at outpatient clinics of five hospitals in Jordan: a cross-sectional study
Ahmad Al-Azayzih, Sayer I. Al-Azzam, Karem H. Alzoubi, Mohammad Shawaqfeh, Majed M. Masadeh
Price
42.00 $
Page No. 425
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 5/2017 (425-432)
Evaluation of drug-prescribing patterns based on the WHO prescribing indicators at outpatient clinics of five hospitals in Jordan: a cross-sectional study
Ahmad Al-Azayzih1, Sayer I. Al-Azzam1, Karem H. Alzoubi1, Mohammad Shawaqfeh1, Majed M. Masadeh2
1Department of Clinical Pharmacy and 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology Irbid, Jordan
Background: Irrational drug prescribing is considered one of the major challenges for the healthcare sectors worldwide, leading to negative outcomes in patients including various drug-related problems, such as polypharmacy, adverse drug events, more demands on drug monitoring, and unwanted increase in treatment cost. Objective: The main objective of this study was to evaluate the trends and issues related to prescription at outpatient hospital pharmacies in Jordan and to contrast that to the WHO rational medication list and WHO drug use indicators. Method: This study was a cross-sectional study, conducted between January 2014 and May 2014. It involved a total number of 24,089 patient encounters from five teaching and referral hospitals in Jordan. The encounters included patients who were prescribed at least one medication during their visit to outpatient clinics in those hospitals. Results: The average number of drugs per prescription was 2.93. The percentage of encounters which had antibiotics or injections in the prescription was 17.7% and 8.1%, respectively. The top three most common prescribed antibiotics were amoxicillin (n = 2,129, 49.9%), ciprofloxacin (n = 609, 14.3%), and clarithromycin (n = 267, 6.3%), while the most common prescribed injections were insulin and insulin analogs (n = 766, 39.2%), cyanocobalamin (Vitamin B12) (n = 612, 31.3%), and erythropoietin (n = 80, 4.1%). The percentage of prescriptions by generic was 57.6%, whereas the prescribing from the essentials drug list (formulary) was close to optimal (99.8%). Conclusion: The average number of prescribed drugs per encounter was higher than what was considered ideal according to WHO standards; the other issue found was a lower percentage of generic prescribing compared to WHO ideal value. The rest of prescribing indicators including the injections prescribing, antibiotics prescribing, and prescribing from the essential drug list were within the optimal range of values recommended by the WHO.
Correspondence to:
Ahmad Al-Azayzih, PharmD, PhD, BCOP
Department of Clinical Pharmacy
Faculty of Pharmacy
Jordan University of Science and Technology
Irbid, 22110, Jordan
Email: [email protected]
Original Research
Effects of five treatment regimens on blood loss and blood transfusion in total knee arthroplasty: a preliminary study in China
Kong-Zu Hu, He-Yan Sun, and Cong Sui
Price
42.00 $
Page No. 433
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 5/2017 (433-441)
Effects of five treatment regimens on blood loss and blood transfusion in total knee arthroplasty: a preliminary study in China
Kong-Zu Hu, He-Yan Sun, and Cong Sui
Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
Objective: Our study is aimed to explore effects of five treatment regimens on blood loss and blood transfusion rate in total knee arthroplasty (TKA) patients. Methods: 191 TKA patients were divided into the rivaroxaban, nadroparin, and tranexamic acid groups (n = 37 each) as well as into the affected-limb-position and tourniquet group (n = 40 each). A 3-month follow-up after operation was needed for all patients. The total blood loss, hidden blood loss, and dominant blood loss were recorded, and hemoglobin and red blood cell changes, pain and knee swelling degrees, hospital for special surgery (HSS), and American knee society (KSS) knee scores were observed. Results: When compared with the rivaroxaban, nadroparin, and tourniquet groups, TKA patients’ dominant blood loss, hidden blood loss, total blood loss, rate and volume of blood transfusion in the tranexamic acid and affected-limb-position groups were significantly decreased. While 7 days after operation, the hemoglobin and red blood cells in the tranexamic acid and affected-limb-position groups were significantly increased. At 1 month and 3 months after operation, when compared with the rivaroxaban, nadroparin, and tourniquet groups, the HSS and KSS scores in the tranexamic acid and affected-limb-position groups were all increased. In comparison with the rivaroxaban, nadroparin, and tourniquet groups, the D-Dimers after operation in the tranexamic acid and affected-limb-position groups were significantly lower. Conclusion: These results demonstrated that for TKA patients, the tranexamic acid and affected-limb-position could obviously reduce the blood loss and blood transfusion rate.
Correspondence to:
Dr. Kong-Zu Hu
Department of Orthopedics
The First Affiliated Hospital of Anhui Medical University
No.218 Jixi Road, Hefei 230022,
Anhui Province, PR China
Email: [email protected]
Case
Report
Pharmacogenomics and tailored polypharmacy: an 80-year-old lady with rosuvastatin-associated rhabdomyolysis and maprotiline-related Ogilvie’s syndrome
Katherina Sreter, Blazenka Barisic, Sanja Popovic-Grle
Price
42.00 $
Page No. 442
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 5/2017 (442-448)
Pharmacogenomics and tailored polypharmacy: an 80-year-old lady with rosuvastatin-associated rhabdomyolysis and maprotiline-related Ogilvie’s syndrome
Katherina Sreter1, Blazenka Barisic2, Sanja Popovic-Grle2
1Department of Clinical Immunology, Pulmonology, and Rheumatology, University Hospital Center “Sestre Milosrdnice”, and 2Clinic for Respiratory Diseases “Jordanovac”, University Hospital Center Zagreb, Zagreb, Croatia
What is known and objectives: Multiple adverse drug reactions (ADRs) are expected, and thus should be prevented in the elderly comorbid patient on polypharmacy. Rosuvastatin is commonly prescribed for the treatment and prevention of atherosclerotic diseases, and in rare cases, is associated with rhabdomyolysis. Maprotiline is a tetracyclic antidepressant, infrequently used in the United States, but seemingly more broadly in European countries. Acute colonic pseudo-obstruction (Ogilvie’s syndrome) caused by maprotiline has thus far, to our knowledge, not yet been described in the literature. Case summary: We present a unique case of synchronous rhabdomyolysis and Ogilvie’s syndrome in an 80-year-old lung cancer survivor following a recent ischemic stroke for which she was prescribed clopidogrel and rosuvastatin for secondary prevention, and maprotiline for post-stroke, new-onset insomnia and anxiety. The ADRs resolved on removal of the offending agents and initiation of conservative treatment. Retrospective pharmacogenetic testing of the patient’s drug-metabolizing enzymes and transporters was performed to guide further management and prevent future potential drug interactions and ADRs. What is novel and conclusions: This is an interesting, albeit unfortunate, complex case that depicts the risk of rare adverse effects to medications and their potential relationship to pharmacogenetics. The impact of anticholinergic side effects of antidepressants on gastrointestinal motility, risk of myopathies with statins, increased susceptibility to ADRs caused by drug-drug interactions, and the utility of pharmacogenomic testing are discussed. The question whether commercially available pharmacogenomic tools are relevant for everyday use to direct patient care and reduce harmful drug-drug interactions is addressed and warrants further research.
Correspondence to:
Katherina Bernadette Sreter, MD
Department of Clinical Immunology, Pulmonology, and Rheumatology
University Hospital Center “Sestre Milosrdnice”
Vinogradska 29, 10 000, Zagreb, Croatia
Email: [email protected]
Case
Report
Delayed de-induction of CYP2C9 compared to CYP3A after discontinuation of rifampicin: Report of two cases
Soichi Shibata, Harumi Takahashi, Akiyasu Baba, Kei Takeshita, Koichiro Atsuda, Hajime Matsubara, Hirotoshi Echizen
Price
42.00 $
Page No. 449
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 5/2017 (449-452)
Delayed de-induction of CYP2C9 compared to CYP3A after discontinuation of rifampicin: Report of two cases
Soichi Shibata1, Harumi Takahashi2, Akiyasu Baba3, Kei Takeshita3, Koichiro Atsuda4#5, Hajime Matsubara1#5, Hirotoshi Echizen6
1Department of Pharmacy, Kitasato University Kitasato Institute Hospital, Tokyo, 2Department of Biopharmaceutics, Meiji Pharmaceutical University, Tokyo, 3Department of Internal Medicine, Kitasato Institute Hospital, Tokyo,
4Department of Pharmacy, Kitasato University Hospital, Sagamihara City, 5Department of Clinical Pharmacy, Center for Clinical Pharmacy and Clinical Sciences, School of Pharmacy, Kitasato University, Tokyo, and
6Department of Pharmacotherapy, Meiji Pharmaceutical University, Tokyo, Japan
Objective: Timely dose reduction of concomitant medications is important after withdrawal of rifampicin, a CYP inducer. However, little is known about the differences in the time course of deinduction for various CYP isoforms. To clarify the time courses of deinduction of CYP2C9 and CYP3A activities after rifampicin withdrawal, we monitored these enzyme activities in 2 patients over time after discontinuing rifampicin. Materials and methods: Two patients (aged 70 and 80 years) received warfarin and rifampicin for anticoagulation and antituberculosis therapy, respectively. Warfarin doses were increased due to rifampicin-induced CYP activity. Upon completion of antituberculosis therapy, rifampicin was discontinued and warfarin doses were titrated downward according to prothrombin time. We monitored CYP2C9 and CYP3A activities over their clinical courses by measuring the metabolic clearance of S-warfarin to S-7-hydroxywarfarin and that of cortisol to 6β-hydroxycortisol, respectively. Results: In both patients, the time courses of CYP2C9 deinduction appeared to be delayed compared to CYP3A. Conclusion: Our findings suggest that a uniform dose reduction protocol for drugs metabolized by different CYP isoforms may be unsafe after rifampicin withdrawal.
Correspondence to:
Soichi Shibata, MSc
Department of
Pharmacy, Kitasato University
Kitasato Institute Hospital
5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan
Email: shibasoh@
insti.kitasato-u.ac.jp
Facies dolorosa
Effects of Danggui Sini decoction on neuropathic pain: experimental studies and clinical pharmacological significance of inhibiting glial activation and proinflammatory cytokines in the spinal cord
Ming Liu, Qiu Hong Qiang, Qian Ling, Chang Xi Yu, Xuejun Li, Suhuan Liu, and Shuyu Yang
Price
42.00 $
Page No. 453
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 55 – No. 5/2017 (453-464)
Effects of Danggui Sini decoction on neuropathic pain: experimental studies and clinical pharmacological significance of inhibiting glial activation and proinflammatory cytokines in the spinal cord
*
Ming Liu1,4, Qiu Hong Qiang4, Qian Ling4, Chang Xi Yu4, Xuejun Li1,2, Suhuan Liu1,3, and Shuyu Yang1,2
1Xiamen Diabetes Institute, 2Division of Endocrinology and Diabetes, 3Central Laboratory, The First Affiliated Hospital of Xiamen University, Xiamen, and 4Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China
Aim: Neuropathic pain responds poorly to drug treatments. Partial relief is achieved in only about half of the patients. Danggui Sini decoction (DSD), an aqueous extract of Angelica sinensis, Ramulus Cinnamomi, and Radix Puerariae, has been used extensively in China to treat inflammatory and ischemic diseases. The current study examined the putative effects of DSD on neuropathic pain. Method: We used two commonly-used animal models: chronic constriction injury (CCI) and diabetic neuropathy for the study. And we examined effects of DSD on pain response, activation of microglia and astroglia in spinal dorsal horn, and expression of proinflammatory cytokines in the spinal cord. Results: Consecutive intragastric administration of DSD (25 – 100 mg/kg) for 10 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models, DSD inhibited the over-expression of specific markers for microglia (Iba-1) and astroglia (GFAP) activation in the spinal dorsal horn. DSD also reduced the elevated nuclear NF-κB level and inhibited the up-regulation of proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. Conclusion: DSD can alleviate CCI and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal dorsal horn. The anti-inflammation effect of DSD may be related to the suppression of spinal NF-κB activation and/or cytokines expression.
Correspondence to:
Prof. Shuyu Yang, MD, PhD,
Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China
Email: [email protected]
