Volume 52, No. 8/2014(August)
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Original Research
Lack of a clinically relevant effect of sugammadex on anti-Xa activity or activated partial thromboplastin time following pretreatment with either unfractionated or low-molecular-weight heparin in healthy subjects
Pieter-Jan De Kam, Annelieke C. Kruithof, Marie-José van Lierop,n Matthijs Moerland, Justin Dennie, Matthew D. Troyer, Ronald B. Langdon, David E. Gutstein, Jacobus Burggraaf, and Rachid El Galta
Price
42.00 $
Page No. 631
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 8/2014 (631-641)
Lack of a clinically relevant effect of sugammadex on anti-Xa activity or activated partial thromboplastin time following pretreatment with either unfractionated or low-molecular-weight heparin in healthy subjects
Pieter-Jan De Kam1, Annelieke C. Kruithof2, Marie-José van Lierop1, Matthijs Moerland2, Justin Dennie1, Matthew D. Troyer1, Ronald B. Langdon1, David E. Gutstein1, Jacobus Burggraaf2, and Rachid El Galta1
1Merck & Co., Inc., Whitehouse Station, NJ, USA, and 2Centre for Human Drug Research (CHDR), Leiden, The Netherlands
Objective: To investigate the potential effect of sugammadex on anti-Xa anticoagulantactivity of enoxaparin and the activated partial thromboplastin time (APTT) of unfractionated heparin (UFH). Methods: This two-part, randomized, double-blind, placebocontrolled, four-period cross-over study was performed in healthy males (18 – 45 years). In each period, subjects received 40 mg enoxaparin (in part 1), 5,000 units UFH (in part 2), or placebo followed by 4 or 16 mg/kg sugammadex, or placebo. Treatments were separated by ≥ 4 days. Primary endpoints were anti-Xa activity and APTT both time-averaged from 3 to 30 minutes post-dose. Geometric mean ratios (GMRs) and their two-sided 90% confidence limits were calculated for anticoagulant plus sugammadex (4 or 16 mg/kg) vs. anticoagulant plus placebo. The pre-specified threshold for a potential effect of clinical relevance was a 90% upper confidence limit (UCL) > 1.50. Results: In part 1 (n = 13), the 90% UCLs were 1.07 and 1.08 for GMRs of anti-Xa activity after dosing with 4 and 16 mg/kg sugammadex, respectively. In part 2 (n = 43), the 90% UCLs for GMRs of APTT were 1.06 and 1.15. Neither sugammadex dose produced a treatment effect that met the pre-specified criterion for potential clinical relevance. Treatments were generally well tolerated. Conclusions: In healthy subjects, treatment with 4 mg/kg and 16 mg/kg sugammadex did not change either anti-Xa activity or APTT to a clinically meaningful extent following pretreatments with enoxaparin or UFH.Correspondence to:
Pieter-Jan De Kam
Merck Sharp & Dohme Corp.
8 Biomedical Grove, Block A, Neuros,
Singapore, 138665, Singapore
Email: [email protected]
Original Research
FOLFIRI and sunitinib as first-line treatment in metastatic colorectal cancer patients with liver metastases – a CESAR phase II study including pharmacokinetic, biomarker, and imaging data
Klaus Mross, Max Scheulen, Dirk Strumberg, Jan Kuhlmann, Friederike Kanefendt, Fritz Sörgel, Ulrich Jaehde, Iris Burkholder, Berta Moritz, and Martin Büchert
Price
42.00 $
Page No. 642
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 8/2014 (642-652)
FOLFIRI and sunitinib as first-line treatment in metastatic colorectal cancer patients with liver metastases – a CESAR phase II study including pharmacokinetic, biomarker, and imaging data
Klaus Mross1, Max Scheulen2, Dirk Strumberg3, Jan Kuhlmann4, Friederike Kanefendt5, Fritz Sörgel6, Ulrich Jaehde5, Iris Burkholder7, Berta Moritz8, and Martin Büchert9
1Tumor Biology Center, Department of Medical Oncology, Freiburg, 2Department Medical Oncology, University Hospital Essen, University Duisburg-Essen, Essen, 3Department Hematology and Oncology, University Hospital Herne, University Bochum, Herne, 4University Medical Center, Internal Medicine II, Freiburg, 5Department of Clinical Pharmacy, Institute of Pharmacy, University Bonn, Bonn, 6IBMP, Institute for Biomedical and Pharmaceutical Research, Nürnberg- Heroldsberg/Institute of Pharmacology, School of Medicine, University of Duisburg- Essen, Essen, 7Department of Nursing and Health, University of Applied Sciences of the Saarland, Zweibrücken, Germany, 8CESAR Central European Society of Anti-Cancer Research-EWIV, Vienna, Austria, and 9Magnetic Resonance Development & Application Center (MRDAC) of the University Medical Center Freiburg, Freiburg, Germany
Background: The aim of this study was the evaluation of pharmacokinetic parameters, biomarkers, clinical outcome, and imaging parameters in metastatic colorectal cancer (mCRC) patients treated with FOLFIRI plus sunitinib. Methods: mCRC patients with liver metastases were treated with FOLFIRI and sunitinib as 1st line therapy. At protocol-defined time points, multicontrast magnetic resonance imaging (MRI)measurements, computed tomography (CT) scans, pharmacokinetics (PK), and biomarker analyses were performed during the first and second treatment cycle. Thereafter, patients were treated until tumor progression, investigator’s decision due to toxicity, or patient withdrawal. Results: 28 patients were screened, 26 were included, and 23 received at least one study medication. Full safety analysis was performed in 23 patients. Full PK and biomarker analyses were performed in 21 patients. Strong responses in tumor size reduction forced a change from the original imaging timing scheme. This unforeseen change in the timing scheme resulted in subgroups too small for meaningful statistical analysis of most imaging parameters. Thus, only a descriptive analysis of the MRI data was possible. In 21/22 patients, MRI showeda decrease of the liver metastases. Best response was partial remission (PR) in 8/17 patients. Plasma concentrations of sVEGFR-2 and sVEGFR-3 decreased in all patients. The majority of the patients developed some kind of toxicity not always deducible to FOLFIRI or sunitinib. Conclusions: Due to the observed side effect profile, FOLFIRI plus sunitinib 37.5 mg per day cannot be recommended for previously untreated mCRC.Correspondence to:
Dr. Martin Büchert
Magnetic Resonance Development & Application Center (MRDAC)
of the University Medical Center Freiburg
Breisacherstraße 60a, 79106 Freiburg, Germany
Email: [email protected]
Original Research
A novel 6-mercaptopurine oral liquid formulation for pediatric acute lymphoblastic leukemia patients – results of a randomized clinical trial
Lidwien M. Hanff, Ron A.A. Mathot, Oscar Smeets, Doerine J. Postma, Satianand Ramnarain, Andras Vermes, Rob Pieters, and C. Michel Zwaan
Price
42.00 $
Page No. 653
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 8/2014 (653-662)
A novel 6-mercaptopurine oral liquid formulation for pediatric acute lymphoblastic leukemia patients – results of a randomized clinical trial
Lidwien M. Hanff1, Ron A.A. Mathot2, Oscar Smeets3, Doerine J. Postma3, Satianand Ramnarain4, Andras Vermes1, Rob Pieters4, and C. Michel Zwaan4
1Department of Hospital Pharmacy, Erasmus MC, Rotterdam, 2Department of Hospital Pharmacy, Academic Medical Center, Amsterdam, 3Laboratory of Dutch Pharmacists, Royal Dutch Pharmacists Association, Den Haag, and 4Department of Pediatric Oncology, Erasmus MC – Sophia Children’s Hospital, Rotterdam, The Netherlands
Objective: Pediatric patients with acute lymphoblastic leukemia (ALL) are treated with oral 6-mercaptopurine (6MP) for nearly 2 years, but no pediatric formulation has been available. In this study, an oral 6MP liquid suitable for pediatric use was developed and tested in the target population. Method: A randomized cross-over study was performed in 20 pediatric ALL patients (age 1.9 – 14.6 years), comparing pharmacokinetics and pharmacodynamics of a newly developed 6MP liquid formulation to 6MP capsules, both taken orally for 4 weeks. Results: Based upon trough levels of the principal active metabolite,6-thioguanine nucleotides (6-TGN),a relative bioavailability of the liquid vs. capsulesof 1.01 was found (90% CI 0.86 – 1.20), demonstrating bioequivalence. This was supported by the similarly observed 6MP dosages needed for leucocyte depletion, for both formulations (35 mg/day (range 10 – 115 mg)). 75% of the parents/patients (p = 0.005) preferred the oral liquid over the capsules because of the ease of administration. Conclusion: We conclude that the novel 6MP liquid is a promising treatment for ALL.Correspondence to:
L.M.Hanff, PharmD, PhD
Department of Hospital Pharmacy Erasmus MC
PO Box 2040, 3000 CA Rotterdam, The Netherlands
Email: [email protected]
Original Research
Therapeutic adherence to osteoporosis treatment
Soňa Tomková, Danica Telepková, Peter Vaňuga, Zdenko Killinger, Ivana Šulková, Peter Celec, and Juraj Payer
Price
42.00 $
Page No. 663
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 8/2014 (663-668)
Therapeutic adherence to osteoporosis treatment
Soňa Tomková1, Danica Telepková2, Peter Vaňuga3, Zdenko Killinger4, Ivana Šulková5, Peter Celec5,6, and Juraj Payer4
1Department of Internal Medicine, P.J. Šafárik University Košice, Hospital KošiceŠaca, 2Private Rheumatology Practice, Košice, 3National Institute of Endocrinology and Diabetology, Ľubochňa, 45th Department of Internal Medicine, Comenius University, University Hospital Bratislava, 5Institute of Molecular Biomedicine, Comenius University, and 6Center for Molecular Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
Objective: Adherence of patients to therapy is a major determinant of therapeutic success, which is not included in most clinical studies. This is especially true for chronic diseases with few subjective symptoms, such as osteoporosis. The aim of our study was to describe and to analyze the therapeutic adherence to several widely used anti-osteoporotic medications in real-world medicine in Slovakia. Methods: Using a retrospective approach, data about drug prescriptions for 8,223 patients from 3 consecutive years were analyzed regarding complianceand persistence. Compliance was measured as medication possession ratio-ratio between the supply of the drugs in the treatment time according to the prescriptions and the time of observation. Persistence was assessed as the percentage of patients who used the drug without a gap for the given time period. Results: The average compliance was 70%, 59%, and 4% for 6, 12, and 24 months, respectively. Average persistence was very low with 54%, 42%, and 22% for 6, 12, and 24 months, respectively. Total average persistence was only 9.8 months. Medications with lower frequency of application tended to be associated with higher adherence. Conclusion: In conclusion, the therapeutic adherence to anti-osteoporotic treatments varies between the available drugs and drug regimens. In general, the adherence is very low but comparable to previously published studies from other countries. This variability of adherence should be considered in clinical decision making together with the variability of therapeutic efficiency found in clinical studies.Correspondence to:
Peter Celec, MD, Dipl. Ing., MSc, PhD, MPH
Institute of Molecular Biomedicine, Comenius University
Sasinkova 4, 811 08 Bratislava, Slovakia
Email: [email protected]
Original Research
Flurbiprofen improves dysfunction of T-lymphocyte subsets and natural killer cells in cancer patients receiving post-operative morphine analgesia
Jin-Chun Shen, He-Liang Sun, Ming-Qiang Zhang, Xiao-Yu Liu, Zhong-Yun Wang, and Jian-Jun Yang
Price
42.00 $
Page No. 669
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 8/2014 (669-675)
Flurbiprofen improves dysfunction of T-lymphocyte subsets and natural killer cells in cancer patients receiving post-operative morphine analgesia
Jin-Chun Shen1, He-Liang Sun1, Ming-Qiang Zhang1, Xiao-Yu Liu1, Zhong- Yun Wang2, and Jian-Jun Yang1
1Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, and 2Department of Anesthesiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
Objective: Acute pain can lead to immune dysfunction, which can be partly ameliorated by successful pain management. Opioids, which are widely used for analgesia, can result in the deterioration of immune function. This study aimed to investigate the influence of morphine with or without flurbiprofen as post-operative analgesics on the immune systems of patients undergoing gastric cancer surgery. Methods: 60 patients undergoing gastric cancer surgery were equally randomized into two groups. They received post-operative patient-controlled intravenous (IV) analgesia using morphine either with or without flurbiprofen. Visual analogue scale (VAS) scores, Bruggemann comfort scale (BCS) scores, morphine consumption, time of first flatus, incidence of nausea/vomiting, and T-lymphocyte subsets (CD3+, CD4+, and CD8+) and natural killer cells (CD3–CD16+CD56+) were evaluated. Results: No significant difference was observed in the VAS scores, BCS scores, and nausea/vomiting incidence between groups. Less morphine was consumed and the time of first flatus was earlier in patients receiving morphine with flurbiprofen than morphine alone. The expression of CD3+, CD4+, CD4+/CD8+, and CD3–CD16+CD56+ decreased at 2 hours after incision and, except for CD3–CD16+CD56+, returned to baseline at 120 hours after surgery. Moreover, the expression of CD3–CD16+CD56+ at 2 hours after incision and the expression of CD3+, CD4+, CD4+/CD8+, and CD3–CD16+CD56+ at 24 hours after surgery were higher in patients receiving morphine with flurbiprofen than morphine alone. Conclusion: The combination of morphine and flurbiprofen ameliorates the immune depression in Tlymphocyte subsets and natural killer cells and provides a similar analgesic efficacy to morphine alone in patients undergoing gastric cancer surgery.Correspondence to:
Dr. Jian-Jun Yang
Department of Anesthesiology
Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, China
Email: [email protected]
Original Research
Development of a population pharmacokinetic model to describe olmesartan medoxomil/ hydrochlorothiazide (20/12.5 mg) FDC tablet in male healthy South Korean subjects
Jung-woo Chae, In-hwan Baek, Jeong-won Seo, Sang-hoon Jung, Hyun-moon Back, Byung-jeong Song, Byung-yo Lee, Hwi-yeol Yun, Wonku Kang, and Kwang-il Kwon
Price
42.00 $
Page No. 676
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 8/2014 (676-683)
Development of a population pharmacokinetic model to describe olmesartan medoxomil/ hydrochlorothiazide (20/12.5 mg) FDC tablet in male healthy South Korean subjects
Jung-woo Chae1*, In-hwan Baek2*, Jeong-won Seo3, Sang-hoon Jung4, Hyun-moon Back1, Byung-jeong Song1, Byung-yo Lee1, Hwi-yeol Yun1, Wonku Kang5, and Kwang-il Kwon1
1College of Pharmacy, Chungnam National University, Daejeon, 2College of Pharmacy, Kyungsung University, Busan , 3Pharmaceutical Standardization Research & Testing Division, Ministry of Food and Drug Safety, Chungcheongbukdo, 4Novo nordisk, Seoul, and 5College of Pharmacy, Yeungnam University, Kyoungbuk, College of Pharmacy, Chung-Ang University, Seoul, South Korea
Aim: The objective of the present study was to develop population pharmacokinetic models for olmesartan medoxomil and hydrochlorothiazide and to investigatem the influence of demographic factors on these population pharmacokinetics. Methods: Plasma concentrations of olmesartan medoxomil and hydrochlorothiazide were measured in 41 healthy volunteers enrolled in our bioequivalence study by LC-MS/MS following oral administration of an olmesartan medoxomil/hydrochlorothiazide (20/12.5 mg) fixed-dose combination tablet. This data and covariates were subjected to nonlinear mixed-effect modeling analysis using the NONMEM software. Evaluation featured a visual predicted check and bootstrapping. Results: The distributions of olmesartan medoxomil and hydrochlorothiazide were best fitted using a two-compartment model with no lag time and first-order elimination. When analyzing hydrochlorothiazide kinetics, we found that TCHO and CL/F were correlated, while. HB and Ka influenced olmesartan medoxomil modeling. All evaluations indicated that the pharmacokinetic profiles of olmesartan medoxomil and hydrochlorothiazide were adequately described using our PPK model. Conclusions: This study indicates that demographic factors influence the inter-individual variability in the disposition of the combination drug, and it might be more useful to apply it to the PK of olmesartan medoxomil/hydrochlorothiazide (20/12.5 mg) FDC tablets administered to patients with hypertension.
*These two authors contributed equally to this work.Correspondence to:
Wonku Kang, PhD
College of Pharmacy, Yeungnam University
Kyoungbuk, 712-249, South Korea
or
Kwang-il Kwon, PhD
College of Pharmacy, Chungnam National University
Daejeon, 305-764, South Korea
Email: [email protected] or [email protected]
Original Research
Population pharmacokinetics of oxcarbazepine active metabolite in Chinese children with epilepsy
Jing Peng, Hua-nian Zhang, Zhi-sheng Liu, Hua Xu, and Yang Wang
Price
42.00 $
Page No. 684
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 8/2014 (684-692)
Population pharmacokinetics of oxcarbazepine active metabolite in Chinese children with epilepsy
Jing Peng1, Hua-nian Zhang1, Zhi-sheng Liu2, Hua Xu1, and Yang Wang1
1Department of Clinical Pharmacology Research Lab, and 2Department of Pediatric Neurology, Wuhan Children’s Hospital, Wuhan, Hubei, China
Objective: This study was to establish the population pharmacokinetic (PPK) model of pharmacologically active metabolite of oxcarbazepine (OXC) and to estimate PPK parameters for the optimal individuation administration of OXC inChinese children with epilepsy. Methods: The pharmacologically active metabolite, 10-monohydroxy derivative of OXC (MHD)was used as the analytical target for monitoring therapy of OXC. A total of 840 MHD serum samples from 466 children with epilepsy were analyzed using high-performance liquid chromatography with UV detection. Patients’ clinical data were retrospectively collected. Population pharmacokinetics analysis was performed using a non-linear mixed-effect model with Phoenix NLME 1.2. Pharmacokinetic parameters were estimated according to a one-compartment model with first-orderabsorption and elimination. Effects of age,gender, total body weight (TBW), daily doseper weight (DDPW) and use of concomitantantiepileptic drugs (AEDs) were analyzed.Bootstrap and predictive check were used simultaneouslyto validate the final populationpharmacokinetics models. Results: The finalPPK model of MHD was: Ka = 0.645 h–1, V(L) = (11.3 + (age – 90.5) × 0.0282 + (TBW– 25.0) × 0.402) × e0.0689, CL (L/h) = (0.557 + (DDPW – 20.8) × 0.00367 + (gender) × (–0.0636)) × e0.120. The final PPK model was demonstrated to be suitable and effective by the bootstrap and predictive check. Conclusions: A PPK model of MHD in Chinesechildren with epilepsy was successfully established. PPK parameters of MHD could be predicted accurately by this model. Thismodel may be very useful for establishingindividual dosage guidelines of OXC in Chinesechildren with epilepsy.Correspondence to:
Dr. Hua-nian Zhang
Department of Clinical Pharmacology Research Lab
No.100 Xianggang Road, Jiang’an District
Wuhan Children’s Hospital, Wuhan, Hubei, China 430016
Email: [email protected]
Original Research
Absence of clinically relevant cardiovascular interaction upon add-on of mirabegron or tamsulosin to an established tamsulosin or mirabegron treatment in healthy middle-aged to elderly men
Marcel van Gelderen, Reiner Tretter, John Meijer, Caroline Dorrepaal, Shanti Gangaram-Panday, Ashley Brooks, Walter Krauwinkel, and James Dickinson
Price
42.00 $
Page No. 693
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 8/2014 (693-701)
Absence of clinically relevant cardiovascular interaction upon add-on of mirabegron or tamsulosin to an established tamsulosin or mirabegron treatment in healthy middle-aged to elderly men
Marcel van Gelderen1, Reiner Tretter2, John Meijer1, Caroline Dorrepaal3, Shanti Gangaram-Panday1, Ashley Brooks4, Walter Krauwinkel1, and James Dickinson1
1Global Clinical Pharmacology and Exploratory Development, Astellas Pharma Europe B.V., Leiden, 2Global Data Science, Astellas Pharma Europe B.V., Leiden, 3Global Medical Science, Astellas Pharma Europe B.V., Leiden, The Netherlands, and 4Covance Clinical Research Unit, Springfield House, Leeds, United Kingdom
Objective: Tamsulosin and mirabegron may be used concomitantly in patients with lower urinary tract symptoms. Since α1-adrenoceptor antagonists are associated with cardiovascular side effects, potential pharmacokinetic and cardiovascular interactions were evaluated. Materials and methods: This was an open-label, randomized, 2-arm, 2-sequence study in 48 healthy men (24/arm) aged 44 – 72 years. In arm 1, subjects received single-dose tamsulosin hydrochloride modified release capsules (0.4 mg) alone and with steady-state mirabegron oral controlled absorption system tablets (100 mg once daily) in random sequence. In arm 2, subjects received single-dose mirabegron alone and with steady-state tamsulosin. Samples for mirabegron and tamsulosin plasma concentrations were collected. Blood pressure (BP) and pulse rate (PR) were measured and orthostatic stress tests were performed. Results: Mirabegron increased tamsulosin Cmax to 159% (90% confidence interval (CI) 143 – 177%), AUC∞1/2 to 116%. Tamsulosin reduced mirabegron Cmax to 85% (90% CI 71 – 103%) and AUC∞ to 84% (90% CI 74 – 95%) without effect on t1/2. Mirabegron and tamsulosin co-treatment caused no statistically significant changes (p > 0.05) in PR or systolic BP versus mono-treatment up to 12 hours post-dose. Mean diastolic BP decreases of –2.1 (95% CI –4.1, –0.1) to –4.2 (–7.5, –0.9) mmHg in arm 1 and –3.0 (–5.7, –0.3) to –4.2 (–7.4, –1.0) mmHg in arm 2 were observed, statistically significant (p < 0.05) at several time points, not accompanied by orthostatic symptoms or increases in positive orthostatic stress tests. Adverse and orthostatic events were balanced across treatments. Conclusions: The observed pharmacokinetic interactions upon add-on of mirabegron or tamsulosin to existing tamsulosin or mirabegron therapy did not cause clinically relevant changes in cardiovascular safety or safety profiles.Correspondence to:
Marcel van Gelderen, PhD
PO Box 344, 2300 AH Leiden, The Netherlands
Email: [email protected]
Original Research
Chemosensitivity of resistant colon cancer cell lines to lobaplatin, heptaplatin, and dicycloplatin
Wen Wei, Zhen Liu, Xi Chen, and Feng Bi
Price
42.00 $
Page No. 702
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 8/2014 (702-708)
Chemosensitivity of resistant colon cancer cell lines to lobaplatin, heptaplatin, and dicycloplatin
Wen Wei1,2, Zhen Liu1, Xi Chen1, and Feng Bi1
1Department of Abdominal Oncology, Cancer Center, West China Hospital, and 2Department of Chemotherapy, Sichuan Cancer Hospital, Chengdu, Sichuan, China
Purpose: Lobaplatin, heptaplatin, and dicycloplatin are three new platinum drugs. The aim of this study is to investigate the chemosensitivity of resistant colon cancer cell lines to these three drugs. Methods: Eight resistant colon cancer cell lines (four oxaliplatin-resistant colon cancer cell lines and four irinotecan-resistant colon cancer cell lines) were cultured in 96-well plates. Lobaplatin, heptaplatin, and dicycloplatin were added in various concentrations. IC50 was determined by MTT assay and the results were confirmed by CCK-8 assay. A cell death detection ELISA assay was performed to quantitate the apoptotic index by detecting the histone-associated DNA fragments generated by the apoptotic cells. Results: Lobaplatin and heptaplatin had an inhibiting effect in all resistant cell lines, dicycloplatin demonstrate only weak antitumor activity in vitro. Conclusions: We confirmed the efficacy of two platinum drugs to oxaliplatin/ irinotecan-resistant colon cancer cell lines, suggesting these two drugs could be considered for improving the control of recurrent colon cancer following initial therapy with oxaliplatin and irinotecan.Correspondence to:
Prof. Feng Bi
Department of Abdominal Oncology
Cancer center, West China Hospital
Sichuan University, Chengdu 610041, China
Email: [email protected]
Review
Pregabalin’s abuse potential: a mini review focusing on the pharmacological profile
Georgios Papazisis and Dimitrios Tzachanis
Price
42.00 $
Page No. 709
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 52 – No. 8/2014 (709-716)
Pregabalin’s abuse potential: a mini review focusing on the pharmacological profile
Georgios Papazisis1 and Dimitrios Tzachanis2
1Department of Pharmacology and Clinical Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece, and 2Cedars-Sinai Medical Center, Los Angeles, CA, USA
Pregabalin, an analogue of the γ-aminobutyric acid mammalian neurotransmitter and its structurally related compound gabapentin are known as α2δ ligands. They might act as inhibitory modulators of neuronal excitability that reduce ectopic neuronal activation of hyperexcited neurons while normal activation remains unchanged. However, the interaction with Ca2+ channel α2δ subunit is not sufficient to account for the broad clinical spectrum of pregabalin effects including the abuse potential. Pregabalin is approved for the treatment of partial epilepsy; generalized anxiety disorder; peripheral< and central neuropathic pain and fibromyalgia. Its prescribing is rapidly increasing and total sales of the drug worldwide reached 4.6 billion US$ in 2012. Since entering widespread clinical use, reports of pregabalin abuse appeared more often, usually involving individuals with a history of abuse of other medications. The purpose of this mini review is to present available published data signaling pregabalin’s abuse liability reflecting on the pharmacological characteristics that might enable this agent to trigger addictive behaviors.Correspondence to:
Georgios Papazisis MD, PhD
Assistant Professor of Pharmacology and Clinical Pharmacology
Department of Pharmacology and
Clinical Pharmacology School of Medicine
Aristotle University of Thessaloniki
P. Levanti 3, 54636 Thessaloniki, Greece
Email: [email protected]
