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Abstract

P. Ay, A. Akici and H. Harmanci

¹Department of Public Health, and ²Department of Pharmacology and Clinical Pharmacology, School of Medicine, Marmara University, Istanbul, Turkey
Objective: This study investigates drug utilization and estimates the prevalence of potentially inappropriate drug use in a Turkish population aged 70 years or older. Material and methods: A cross-sectional study was carried out on a total of 1,019 participants who accepted face-to-face questionnaires in home interviews in Istanbul. All medications used in the three weeks prior to the study were recorded. Some major risk factors that might influence the use of inappropriate medication such as socio-demographic characteristics and concomitant disease such as depression and dementia were also questioned. Inappropriate drug use was assessed using the Beers criteria. Results: Among the 1,019 participants, 903 (88.6%) had been using at least one medication during the last three weeks. The average number of medications used was 2.9 Correspondence to:
P. Ay, MD Marmara Universitesi Tip Fakultesi, Halk Sagligi Anabilim Dali Tibbiye Cad. No. 34716 Haydarpasa Istanbul, Turkey
Email: aypinar@hotmail.com

Abstract

Y. Nakazono, H. Abe, H. Murakami, N. Koyabu, Y. Isaka, Y. Nemoto, S. Murata, Y. Tsutsumi, H. Ohtani and Y. Sawada

¹Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, and
²Department of Psychiatry, Ongata Hospital, Tokyo, Japan
The aim of the present study is to examine the relationship between dopamine D2-receptor gene (DRD2) polymorphisms (Taq1A, Taq1B, –141C Ins/Del) and the risk of extrapyramidal adverse effects (EPS), assessed according to the Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), or the maintenance dose of antipsychotics in schizophrenic patients. The DIEPSS score was significantly higher in patients bearing the –141C Del allele than in those without it. Taq1A and Taq1B restriction fragment length polymorphisms (RFLPs) did not significantly affect the DIEPSS score. On the other hand, maintenance doses of neuroleptics and antiparkinsonian drugs were significantly higher in patients with the B1 allele of Taq1B RFLP than in those without it, while the Taq1A RFLP and –141C Ins/Del polymorphisms were not significantly related to the maintenance doses. In conclusion, the risk of EPS may be increased in patients with the –141C Del allele of the DRD2 gene. In these patients, antipsychotics should be administered with caution.Correspondence to:
Prof. Y. Sawada
Graduate School of Pharmaceutical Sciences
Kyushu University
3-1-1 Maidashi, Higashi-Ku
Fukuoka 812-8582, Japan
Email: sawada@phar.kyushu-u.ac.jp

Abstract

N. Cranswick¹, J. Turzíková², M. Fuchs² and R. Hulhoven³

¹Royal Children’s Hospital and Murdoch Children’s Research Institute, University of Melbourne, Australia, ²Pediatric Department of Faculty Hospital Bulovka, Prague, Czech Republic and ³UCB S.A. – Pharma Sector, Braine-l’Alleud, Belgium
Background: Levocetirizine is an antihistamine with high affinity and selectivity for H1-receptors, which exhibits an excellent benefit/risk ratio in the treatment of allergic rhinitis and urticaria. This is the first study performed with this drug in very young children. Objective: The aim of this study was to confirm the intended regimen of levocetirizine (0.125 mg/kg twice a day) for further studies in children aged 12 – 24 months. Material and methods: The pharmacokinetic/ pharmacodynamic profile of levocetirizine was studied in 15 toddlers suffering from recurrent cough and other allergy-related symptoms, aged 20.7 ± 3.7 months, and treated twice a day with 0.125 mg/kg for 90 days. A histamine-induced wheal and flare test (W&F) was performed prior to treatment. Blood was sampled at 1, 2, 4, 6, 9 and 12 hours after the first dose. Twelve hours after the evening dose on Days 3 – 6, and on day 90, a histamine-induced wheal and flare test was repeated and a blood sample was taken for trough value assessment. Results: A peak plasma level of 286 ± 68 ng/ml was observed after one hour. The elimination half-life was 4.1 ± 0.7 hours, the apparent body clearance 1.05 ± 0.10 ml/min/kg, and the apparent volume of distribution 0.37 ± 0.06 l/kg. Morning trough values at Days 3 – 6, and at Day 90 were respectively 78 ± 30 ng/ml and 110 ± 86 ng/ml. The median inhibition of the wheal was 100% at Days 3 – 6, and Day 90. That of the flare was 99.6% at Days 3 – 6, and 98.9% at Day 90. The overall safety profile of this three-month open study was good. Conclusion: This first study with levocetirizine in children aged 12 – 24 months shows the adequate pharmacokinetic/pharmacodynamic profile and the good safety profile of 0.125 mg/kg levocetirizine given twice a day, which can be proposed for further studies in this age group.Correspondence to:
Dr. R. Hulhoven
UCB S.A. – Pharma Sector
Chemin du Foriest
1420 Braine-l’Alleud, Belgium
Email: reginald.hulhoven@ucb-group.com

Abstract

W. Dieterle¹, J. Mann² and K. Kutz³

¹Drug Disposition Consultants, Lörrach, Germany, ²Clinical Research and Development, Speedel Development AG, Basel, ³AccelPharm, Basel, Switzerland
Background: SPP301 is a competitive antagonist of ET-1 with a high selectivity for the ETA receptor. The multiple-dose pharmacokinetics, pharmacodynamics, safety and tolerability of SPP301 were investigated in healthy male subjects. Methods: In an ascending-dose, double-blind, placebo-controlled trial doses of 5, 20, 40 and 60 mg SPP301 were given orally on Day 1 and, after a wash-out period of 48 hours, once daily for seven days. At regular intervals, blood pressure and pulse rate, plasma levels of ET-1, and of SPP301 and its hydroxymethyl metabolite as well as urinary excretion of the parent drug and its metabolite were determined. Results: SPP301 was generally well-tolerated. With the higher doses asymptomatic and transient increases in liver transaminases were observed. No other clinically relevant effects of SPP301 on hematology, biochemistry or urinalysis parameters were observed. Vital signs, ECG parameters and physical examinations showed no time or treatment effect. The pharmacokinetics of SPP301 and its hydroxymethyl metabolite (Ro 68-5925) were linear up to 40 mg SPP301. Steady state was reached after 3 – 4 days. The apparent terminal half-life of SPP301 and the metabolite was in the range of 7 – 10 hours after single and repeated doses. At the 60 mg dose level plasma concentrations of SPP301 decreased from the first to the last day of oral treatment. The average decreases in Cmax and AUC were 33% and 37%, respectively. Cmax and AUC of the metabolite amounted to about 4 – 6% of the values for SPP301 under single and repeated-dose conditions. Urinary excretion of SPP301 and of its metabolite were below 0.1% and 5%, respectively. Conclusion: SPP301 is quite well-tolerated, pharmacokinetics are linear and time-independent up to 40 mg multiple doses. Steady state is reached after 3 – 4 days. Urinary excretion of the unchanged drug plays a minor role in the elimination process of SPP301. ET-1 plasma concentrations increased about 1.5-fold at 20 mg and all further doses.
Correspondence to:
Dr. J. Mann
Speedel Development AG
Department of Clinical Research and Development
Hirschgässlein 11
4051 Basel, Switzerland
Email: jessica.mann@speedel.com

Abstract

J.J. Lima, B. Nhi Beasley, R.B. Parker and J.A. Johnson

¹Center for Clinical Pediatric Pharmacology & Pharmacogenetics, Nemours Children?s Clinic, Jacksonville, FL, ²University of Tennessee College of Pharmacy, Memphis, TN, ³Food and Drug Administration, Center for Drug Evaluation and Research, Rockville, MD,
Objective: To formulate and evaluate a pharmacodynamic model that characterizes the effects of S-verapamil on the circadian 24-hour ambulatory blood pressure (ABP). Methods: ABP was recorded in 19 hypertensive patients off drug, and following administration of the targeted dose of COER-V given once daily for at least 30 days. Blood samples were collected after the last dose for determination of the pharmacokinetic of S-verapamil. ABP vs. time was analyzed using a cosinor function, and the effects of S-verapamil on ABP were fitted using the pharmacodynamic model. Results: COER-V decreased average systolic and diastolic blood pressures (mesors): baseline, 142 Correspondence to:
J.J. Lima, Pharm. D. Center for Clinical Pediatric Pharmacology & Pharmacogenetics Nemours Children?s Clinic 807 Nira Street Jacksonville, FL 32207, USA
Email: Jlima@nemours.org

Abstract

C. Pistos, C. Astraka, M. Kalovidouris, E. Vassilopoulos

¹Independent Research and Laboratory Solutions, and ²Specifar Pharmaceuticals, Athens, Greece
Objective: This paper describes a bioequivalence study with two oral glimepiride (4 mg) tablets formulations. The reference preparation was Solosa/Aventis Pharmaceuticals Inc., USA, and the test preparation was Glimepiride/Specifar, Athens, Greece. Subjects, material and methods: The study design was open, randomized, two-period, two-sequence, two-treatment with crossover involving 24 healthy male and female subjects. All subjects completed the study. Glimepiride plasma concentrations were measured utilizing a sensitive, reproducible and accurate HPLC method. Pharmacokinetic parameters used to assess bioequivalence were AUC_0-last, AUC_0-inf for the extent of absorption and C_max and t_max for the rate of absorption. Statistical evaluation of C_max, AUC_0-last, and AUC_0-inf was done after semi-logarithmic transformation using a two-way analysis of variance (ANOVA). T_max values were tested using the distribution-free Hodges-Lehman interval. Results and conclusion: The parametric 90% confidence intervals for ratio T/R ranged from 90.60 ? 108.00% (point estimate 98.90%) for AUC_0-last, 90.70 ? 107.90% (point estimate 98.90%) for AUC_0-inf and 86.70 ? 103.70% (point estimate 94.80%) for C_max, respectively. Based on the results of t_max, K_el and t_1/2, there were no statistically significant differences and the two glimepiride preparations are equivalent with respect to rate and extent of absorption as defined by the European Union bioequivalence requirements.Correspondence to:
Dr. C. Pistos Independent Research and Laboratory Solutions 240 Klisthenous Str. 153 44, Gerakas, Athens, Greece
Email: cpistos@ilsgr.com

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Volume 43, No. 4/2005(April)