Volume 48, No. 6/2010(June)
|
 Int. Journal of Clinical Pharmacology and Therapeutics
The online-version will be updated before the print-version of this Journal is published. Upon request we will send the password and user name by e-mail. The online-service is only available for subscribers of the print-version, if proof of purchase is submitted.
The use of the online-version will be charged with an extra fee (additional to the subscription of the print-version).
The service can be used until December 31st of the year of subscription.
|
| Full Issue Price: 30.00$ |
 |
Editorial
Critical questions concerning nifedipine extended release formulations
B.G. Woodcock
Abstract
Critical questions concerning nifedipine extended release formulations
Original Research
Pharmacokinetic modeling of the dosing interval dependency for the interaction between itraconazole and triazolam
A. Toi, H. Ohtani, M. Tsujimoto and Y. Sawada
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 48– No. 6/2010 (356-366)
Pharmacokinetic modeling of the dosing interval dependency for the interaction between itraconazole and triazolam
A. Toi1, H. Ohtani2, M. Tsujimoto3 and Y. Sawada4
1Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, 2Keio University Faculty of Pharmacy, Tokyo, 3Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Kyoto, and 4Laboratory of Drug Informatics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
Objective: Itraconazole is a potent inhibitor of cytochrome P450 (CYP) 3A with an elimination half-life of more than 30 hours. Therefore, itraconazole may cause persistent CYP3A inhibition. Triazolam is primarily metabolized by CYP3A and its plasma concentration is increased remarkably by itraconazole. Although separating their dosages by 24 hours has been shown to reduce the interaction, an appropriate dosage interval remains to be determined. The aim of this study was to identify an appropriate dosage schedule to avoid their interaction. Materials and methods: We developed a pharmacokinetic model based on the assumption that both itraconazole and hydroxyitraconazole competitively and reversibly inhibit the first-pass metabolism and systemic elimination of triazolam. The developed model was simultaneously fitted to the plasma concentration profiles of triazolam, taken from the literature, by using the plasma concentration-time profiles of itraconazole and hydroxyitraconazole as input functions to estimate their in vivo Ki values. Subsequently, we simulated the plasma concentration profiles of triazolam administered after itraconazole therapy with various dosing intervals. Results: The model could explain and simulate the interaction between itraconazole-triazolam using a variety of dosage intervals between the administrations. Conclusions: The developed model may provide useful information with regard to the appropriate interval for triazolam administration during itraconazole therapy.Correspondence to:
Prof. Y. Sawada, PhD
Graduate School of Pharmaceutical Sciences
The University of Tokyo
7-3-1 Hongo, Bunkyo-ku
Tokyo, 113-0033 Japan
Email: sawada@mol.f.u-tokyo.ac.jp
Original Research
Effect of linagliptin (BI 1356) on the steady-state pharmacokinetics of simvastatin
U. Graefe-Mody, S. Huettner, H. Stähle, A. Ring and K.A. Dugi
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 48 – No. 6/2010 (367-374)
Effect of linagliptin (BI 1356) on the steady-state pharmacokinetics of simvastatin
U. Graefe-Mody1, S. Huettner1, H. Stähle1, A. Ring1 and K.A. Dugi2
1Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/Riss and 2Boehringer Ingelheim GmbH, Ingelheim, Germany
Objective: This study was conducted to investigate any potential effect of the dipeptidyl peptidase-4 inhibitor linagliptin (which is being developed to improve glycemic control in patients with Type 2 diabetes) on the pharmacokinetics of simvastatin (a lipid-lowering, HMG-CoA reductase inhibitor). Methods: This open-label, multiple-dose study was conducted in 20 healthy male Caucasian subjects. Simvastatin (40 mg/day) was administered alone for 6 days, followed by co-administration with linagliptin (10 mg/ day) for 6 days, followed by simvastatin single administration for a further 8 days. Plasma concentrations of simvastatin and its active metabolite simvastatin Β-hydroxy acid were determined on Day 6 (before co-administration of linagliptin) and Days 12, 16 and 20 (after co-administration of linagliptin). Results: The geometric mean ratio (GMR) (90% confidence interval (CI)) following co-administration of linagliptin with simvastatin (Day 12) compared with administration of simvastatin alone (Day 6) for simvastatin AUC was 134.2% (119.4, 150.7) and for simvastatin acid AUC was 133.3% (118.1, 150.3). The GMR (90% CI) for simvastatin Cmax,ss was 110.0% (89.3, 135.6) and for simvastatin acid Cmax,ss was 120.7% (101.5, 143.6). 20 adverse events were reported by 11 subjects. Both simvastatin and linagliptin were well tolerated. Conclusions: Linagliptin-mediated effects on simvastatin exposure are not considered to be clinically relevant in terms of patient tolerability or safety. Therefore, a dose adjustment of linagliptin is not necessary when these two agents are administered together and linagliptin co-administration is not expected to exert a clinically relevant effect on the pharmacokinetics of other CYP3A4 substrates.Correspondence to:
Dr. U. Graefe-Mody
Therapeutic Area Metabolism
Boehringer Ingelheim Pharma GmbH and Co. KG
Birkendorfer Str. 65
88397 Biberach/Riss, Germany
Email: Ulrike.Graefe-Mody@boehringer-ingelheim.com
Original Research
Population pharmacokinetics of tacrolimus in kidney transplant patients
R. Velickovic-Radovanovic, A. Catic-Djordjevic, J.R. Milovanovic, V. Djordjevic, G. Paunovic and S.M. Jankovic
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 48 – No. 6/2010 (375-382)
Population pharmacokinetics of tacrolimus in kidney transplant patients
R. Velickovic-Radovanovic1, 2, A. Catic-Djordjevic1, J.R. Milovanovic3, V. Djordjevic2, G. Paunovic2 and S.M. Jankovic3
1Pharmacy Department, Medical Faculty, University of Nis, 2Clinic of nephrology and haemodialysis, Clinical centre Nis, Nis, and 3Pharmacology Department, Medical Faculty, University of Kragujevac, Kragujevac, Serbia
Objective: The purpose of this study was to derive population pharmacokinetics (PPK) model of tacrolimus clearance, identify and describe factors that influence it in Serbian kidney transplant patients. Methods: Population pharmacokinetics analysis was performed using nonlinear mixed-effects model (NONMEM) program from Serbian adult kidney transplant patients receiving triple immunosuppressive therapy, including oral tacrolimus. Details of drug dosage history, sampling time and tacrolimus concentration in 63 patients (44 males and 19 females), 27 – 57 years old (age mean 40.88 ± 7.01 years) were collected retrospectively. Effects of several covariates on tacrolimus clearance were tested: total body weight, gender, age, posttransplantation days, hemoglobin count, CRP, alanine aminotransferase/aspartate aminotransferase, total daily dose of tacrolimus, co-medication with cotrimoxasole, omeprazole, mycophenolate mofetil and prednisone (> 25 mg). Results: Typical mean value of tacrolimus clearance, estimated by the base model (without covariates), in our population was 1.03 l h–1. The final model showed that tacrolimus clearance increased with total daily dose and concomitant administration of high-dose prednisone (> 25 mg). The magnitude of prednisone effect was + 1.16 l h–1. Final model was validated in a group of 17 patients, showing good predictive performance. Conclusions: The derived model describes well tacrolimus clearance in terms of characteristics of Serbian kidney transplant patients, offering basis for rational individualization of tacrolimus dosing regimens.Correspondence to:
J.R. Milovanovic
Pharmacology Department
Medical Faculty
University in Kragujevac
34000 Kragujevac, Serbia
Email: Jasminamilo@yahoo.com
Original Research
Efficacy and tolerability of paliperidone ER and other oral atypical antipsychotics in schizophrenia
M.P. Jones, D. Nicholl and K. Trakas
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 48 – No. 6/2010 (383-399)
Efficacy and tolerability of paliperidone ER and other oral atypical antipsychotics in schizophrenia
M.P. Jones1, D. Nicholl2 and K. Trakas3
1Psychology Department, Macquarie University, Australia, 2Johnson & Johnson Pharmaceutical Services, LLC, Raritan, NJ, USA, 3Janssen-Ortho, Inc., Toronto, ON, Canada
Atypical antipsychotics are widely used in the pharmacologic management of schizophrenia. Information to guide evidence-based clinical decision making must be continually updated, particularly as new clinical trial data and new antipsychotic agents become available. Objective: This meta-analysis of oral atypical antipsychotics assessed the relative effectiveness and tolerability profile of a recently introduced agent, paliperidone extended-release (ER), to determine its place within the efficacy and tolerability spectrum of the labeled dose ranges of other oral atypical antipsychotics. Methods: Randomized placebo-controlled studies of risperidone, olanzapine, quetiapine, and aripiprazole were identified via database search (MEDLINE, EMBASE, Cochrane Library, PsycInfo, and Cumulative Index to Nursing & Allied Health Literature). Baseline demographic, efficacy, and safety data were extracted and combined in meta-analysis. Random effects meta-regression assessed potential confounding by patient mean age, gender ratio, and duration of therapy on variability in efficacy and safety. Results: Within the spectrum of efficacy and safety of the class, paliperidone ER demonstrated a novel efficacy-tolerability profile versus the other oral atypical antipsychotics, including lower odds of withdrawal for any reason and less weight gain. Odds of withdrawal due to adverse events were lower with paliperidone ER compared with risperidone and with atypical antipsychotics as a class. Paliperidone ER was associated with lower odds of somnolence and agitation than the atypical class as a whole and with lower odds of weight gain than all of the atypical antipsychotics, including risperidone. The main factor in the observed variability in efficacy results between studies was the antipsychotic, rather than patient-related factors or duration of therapy. Conclusions: Paliperidone ER is an effective and well-tolerated oral atypical antipsychotic that provides an important new treatment option for patients with schizophrenia. Owing to the heterogeneity within the class, information on individual benefit/risk profiles of antipsychotics is necessary for selecting an appropriate treatment for each patient.Correspondence to:
A/Prof. M.P. Jones
Psychology Department, C3A 520
Macquarie University
North Ryde NSW 2109, Australia
Email: Mike.Jones@psy.mq.edu.au
Case Reports
Therapeutically relevant blood pressure differences with two nifedipine (60 mg) osmotic delivery systems of differing design: three case reports
P.T. Pollak
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 48 – No. 6/2010 (400-404)
Therapeutically relevant blood pressure differences with two nifedipine (60 mg) osmotic delivery systems of differing design: three case reports
P.T. Pollak
Departments of Medicine, Cardiac Sciences, and Physiology & Pharmacology, University of Calgary, Calgary, Canada
During the introduction of a new once-daily nifedipine 60 mg osmotic delivery tablet to Canada in 2009, several patients previously maintained at target blood pressure on regimens that included nifedipine 60 mg daily were observed to have > 10 mmHg rises in their systolic pressure during follow-up. The only difference noted in their medication and clinical status was a substitution with the new 60 mg nifedipine formulation by their pharmacists. Three patients agreed to report home blood pressure for N of 1 studies in which all clinical parameters remained the same, but their nifedipine was repeatedly switched between the original and alternate formulations each week. Of 14 recorded switches, systolic pressure was higher on the alternate formulation 13 times. In at least some patients, the alternate pump technology appears less effective. This highlights the need for better bioequivalence criteria for comparing differing delivery technologies that artificially retard absorption of the drug.Correspondence to:
P. T. Pollak, MD, PhD, FACP
3330 Hospital Dr. NW – 1410 HSC
Calgary, AB, Canada T2N 4N1
Email: amiokinetics@hotmail.com
Letter to the Editor
Critical questions concerning the validity of the Bayer study report of “Differences in bioavailability between 60 mg of nifedipine osmotic push-pull systems after fasted and fed administration”
M.C. Meyer
Abstract
Critical questions concerning the validity of the Bayer study report of “Differences in bioavailability between 60 mg of nifedipine osmotic push-pull systems after fasted and fed administration”
M.C. Meyer
Letter to the Editor
Response to the letter “Critical questions concerning the validity of the Bayer study report of differences in bioavailability between 60 mg of nifedipine osmotic push-pull systems after fasted and fed administration”
H.H. Blume (on behalf of the SocraTec R&D study team)
Abstract
Response to the letter “Critical questions concerning the validity of the Bayer study report of differences in bioavailability between 60 mg of nifedipine osmotic push-pull systems after fasted and fed administration”
H.H. Blume
Letter to the Editor
Response to the letter “Critical questions concerning the validity of the Bayer study report of differences in bioavailability between 60 mg of nifedipine osmotic push-pull systems after fasted and fed administration”
E. Brendel, K. Pauli, A. Pontius and C. Toal on behalf of Bayer
Abstract
Response to the letter “Critical questions concerning the validity of the Bayer study report of differences in bioavailability between 60 mg of nifedipine osmotic push-pull systems after fasted and fed administration”
E. Brendel, K. Pauli, A. Pontius and C. Toal on behalf of Bayer
