Volume 43, No. 8/2005(August)
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 Int. Journal of Clinical Pharmacology and Therapeutics
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Clinical Trial Design
A comparison of placebo and no-treatment during a hypnotic clinical trial
Abstract
W.V. McCall, M.L. Perlis, X. Tu, A.E. Groman, A. Krystal and J.K. Walsh
1Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, 2Sleep and Neurophysiology Research Laboratory, Department of Psychiatry, University of Rochester, 3University of Rochester Medical Center, N
Objective: Sleep parameters commonly improve during placebo treatment in insomnia clinical trials. We examined whether the improvement seen with placebo was related to taking pills or other non-specific factors. Method: 95 insomniacs took either a placebo pill (pill+) or no pill (pill?) on nights of their choosing over 12 weeks. Results: Pills were consumed on about half of the nights. Consistent improvement was seen with reduced reported sleep latency, wakefulness after sleep onset, number of awakenings, and total sleep time over the 12 weeks for both the pill+ and pill? condition. A difference between pill+ and pill? was detected only for total sleep time, and this difference favored pill+. Conclusions: This study suggests that improvement seen during placebo treatment is more related to non-specific factors of participating in clinical trial than to pill taking behavior.Correspondence to:
W.V. McCall, MD, MS
Department of Psychiatry and Behavioral Medicine
Wake Forest University Health Sciences
Medical Center Boulevard
Winston-Salem, NC 27157-1071, USA
Email: vmccall@wfubmc.edu
Therapeutics
Cefepime in critically ill patients: continuous infusion vs. an intermittent dosing regimen
Abstract
B. Georges, J.-M. Conil, P. Cougot, J.-F. Decun, M. Archambaud, T. Seguin, G. Chabanon, C. Virenque, G. Houin and S. Saivin
1Anesthesia Reanimation, 2Pharmacokinetic Laboratory and Toxicologic Clinic, 3Bacteriologic Laboratory, CHU Rangueil, and 4Laboratory of Xenobiotic Kinetics, UMR 181 Experimental Physiopathology and Toxicology (UPTE INRA-ENVT), Faculty of Pharmaceutic Sci
The aim of this study was to compare the pharmacokinetic and pharmacodynamic parameters of a continuous infusion of cefepime vs. an intermittent regimen in critically ill adult patients with Gram-negative bacilli infection. The prospective randomized parallel study was carried out in 50 patients with severe pneumonia (n = 41) or bacteremia (n = 9). They received cefepime 4 g/d either as a continuous infusion or intermittent administration 2 Correspondence to:
Prof. G. Houin
Laboratoire de Pharmacocin
Email: houin.g@chu-toulouse.fr
Pharmacodynamics
D2 dopamine receptor occupancy, risperidone plasma level and extrapyramidal motor symptoms in previously drug-free schizophrenic patients
Abstract
R. Regenthal, U. Kunstler, S. Hesse, O. Sabri and R. Preiss
Departments of 1Clinical Pharmacology and 3Nuclear Medicine, University of Leipzig, Germany, and 2Department of Social and Community Psychiatry, Psychiatric Services of the University of Berne, Switzerland, Department of Psychiatry and Psychotherapy, Diac
Rationale: A relationship between high D2 occupancy (above 80%) and extrapyramidal-motor symptoms under neuroleptic treatment has been observed in several neuroimaging studies. Objectives: We investigated the striatal dopamine D2 receptor occupancy, risperidone plasma level and extrapyramidal-motor symptoms in drug-free schizophrenic patients. Methods: Ten schizophrenic patients were treated with 3 ? 6 mg risperidone daily. After four weeks administration, a [123I]iodobenzamide ([123I]IBZM)-single photon emission tomography (SPET) scan for determination of D2 receptor occupancy was carried out (in eight responders) and compared to a control group. Plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (active moiety) were determined by high performance liquid chromatography and electrochemical detection. Extrapyramidal-motor symptoms were assessed by means of the Simpson-Angus-Scale and a handwriting test before treatment and coincident with the scan. Results: The D2 receptor occupancy (Mean 62%, SD 13%) positively correlated with the plasma level of the risperidone active moiety as well as with the reduction in handwriting area. Multiple linear regression revealed an inherent relationship with a coefficient of determination of r = 0.956 (p = 0.02). No clinical relevant extrapyramidal-motor symptoms were observed. Conclusions: In drug-free schizophrenic responders, the simultaneous assessment of both plasma level and reduction in handwriting area may be a useful clinical tool for a surrogate estimate of D2 receptor occupancy under risperidone treatment. This may help to minimize or even prevent extrapyramidal-motor symptoms.Correspondence to:
Dr. R. Regenthal
Department of Clinical Pharmacology
University of Leipzig
Haertelstra
Email: regenr@medizin.uni-leipzig.de
Pharmacokinetics
Trough levels of mycophenolic acid and its glucuronidated metabolite in renal transplant recipients
Abstract
U. Merkel, S. Lindner, R. Vollandt, H. Sperschneider and A. Balogh
1Institute of Clinical Pharmacology, 2Institute of Medical Statistics,
Computer Science and Documentation, and 3Nephrology,
Department of Internal Medicine, University Hospital, Jena, Germany
Objective: The prophylactic use of the immunosuppressant prodrug, mycophenolate mofetil (MMF) to prevent graft rejection in renal transplant patients is continuing to increase. We measured trough levels of the active metabolite, mycophenolic acid (MPA) and its inactive glucuronide (MPAG) in renal recipients with the aim of characterizing individual variability and of ascertaining factors influencing trough levels, in particular the effect of differences in renal function and the effect of drugs given concurrently. Methods: Laboratory and clinical data obtained in 35 renal recipients treated with triple therapy (MMF, cyclosporin A (CsA), steroids) were included in this retrospective study. Trough levels of MPA and MPAG were obtained after transplantation and up to 16 months post transplantation where the mean observation period was 5.7 months. Plasma levels were measured using a validated HPLC assay. Results: A total of 212 plasma concentrations of MPA and 209 of MPAG were measured. There was considerable intra- and interindividual variability in MPA and MPAG trough levels especially in the early post-transplantation phase. At a fixed dose of 2 g/d MMF, the mean MPA level during the first 30 days averaged 1.46 Correspondence to:
Dr. U. Merkel
Institute of Clinical Pharmacology
University Hospital
07740 Jena, Germany
Email: ute.merkel@med.uni-jena.de
Bioavailability Section
A bioequivalence study of citalopram based on quantification by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry
Abstract
G. Duarte Mendes, N. Carter do Carmo Borges, A. dos Santos Pereira, F. Duarte Mendes, R. Eliseo Barrientos-Astigarraga and G. De Nucci
1Department of Clinical Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), 2Cartesius Development Clinical Research, Campinas, Brazil
Objective: The aim of this study was to compare the bioavailability of two citalopram formulations (citalopram from Eurofarma LaboratCorrespondence to:
Dr. G. De Nucci
Av. Jesuino Marcondes Machado, 415
13092-320, Campinas, SP, Brazil
Email: denucci@dglnet.com.br
Bioavailability Section
Comparative bioavailability of clarithromycin formulations in healthy Brazilian volunteers
Abstract
A.P.D.B. Ruenis, R.A. Moreno, E. Abib-J
1Piracicaba Dental School, State University of Campinas (UNICAMP), Piracicaba, SP, 2Synchrophar Assessoria e Desenvolvimento de Projetos Cl
Objective: To compare the bioavailability of clarithromycin 500 mg tablets (Merck S.A Industrias Quimicas, Sao Paulo, SP, Brazil, used as test formulation) and KlaricidCorrespondence to:
Prof. Dr. F.C. Groppo
Faculdade de Odontologia de Piracicaba
Universidade Estadual de Campinas
Av. Limeira 901
13414-903 Piracicaba, SP, Brazil
Email: fcgroppo@fop.unicamp.br
Laudatio
In celebration of the 65th birthday of Professor Dr. Annemarie Hoffmann (Jena)
Abstract
M. Hippius and K. Farker
Adverse Drug Reactions
Drug-induced gastrointestinal disorders in surgical patients admitted to the University Hospital, Jena, Germany
Abstract
M. Hippius and U. Hegenbart
Letter to the Editor
Appropriateness of benzodiazepine prescribing in general practice
Abstract
E. van Rijswijk, S.M. Zandstra, E.H. van de Lisdonk, F.G. Zitman and C. van Weel
