Volume 49, No. 4/2011(April)
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 Int. Journal of Clinical Pharmacology and Therapeutics
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Editorial
Getting the dose of vancomycin right in the neonate
J.N. van den Anker
Abstract
Getting the dose of vancomycin right in the neonate
J.N. van den Anker
Editorial
The regulation of herbal medicine
E. Ernst
Abstract
The regulation of herbal medicine
E. Ernst
Original Research
Pharmacokinetics of vancomycin in neonates admitted to the neonatology unit at the Jordan University Hospital
E.F. Badran, A. Shamayleh and Y.M. Irshaid
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 49 – No. 4/2011 (252-257)
Pharmacokinetics of vancomycin in neonates admitted to the neonatology unit at the Jordan University Hospital
E.F. Badran1, A. Shamayleh1 and Y.M. Irshaid2
Departments of 1Pediatrics and 2Pharmacology, Faculty of Medicine, University of Jordan, Amman, Jordan
Background: Vancomycin is used in neonatal intensive care units to treat nosocomial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or coagulase-negative staphylococci. Current dosing regimens are not adequate, producing trough concentrations below the target range. Patients and methods: 151 neonates who received vancomycin and had vancomycin peak and trough concentration measurements as part of regular therapeutic drug monitoring were utilized. The patients were divided into three groups according to gestational age; less than 28 weeks, 28 to less than 34 weeks and 34 weeks to term. Neonates were given vancomycin doses as per guidelines. The pharmacokinetic parameters, elimination rate constant (K), elimination half-life (t1/2), volume of distribution (VD) and clearance (CL), were calculated. Results: Peak vancomycin concentrations ranged from 9.4 to 52.8 mg/l, while troughs ranged from 0.0 to 16.6 mg/l. One third of the trough concentrations were below 5 mg/l and are thus, subtherapeutic. There were no statistically significant differences between the three groups in regard to elimination rate constant and half-life. However, there was a statistically significant difference in volume of distribution between the three groups (p < 0.05), and in clearance between the first group and the other two (p < 0.05), using Kruskal-Wallis statistical test. Conclusions: The empirical dosing method used was inadequate in one third of patients. Individualization of vancomycin dosing in the neonatal critical care unit at The Jordan University Hospital seems necessary.Correspondence to:
Y. Irshaid, MD, PhD, ABCP
Department of Pharmacology
Faculty of Medicine
The University of Jordan
Amman 11942, Jordan
Email: yacoub.irshaid@yahoo.com; y.irshaid@ju.edu.jo
Original Research
Single-dose pharmacokinetics, pharmacodynamics and safety of AZD0837, a novel oral direct thrombin inhibitor, in young healthy male subjects
S. Johansson, M. Cullberg, U.G. Eriksson, M. Elg, K. Dunér, E. Jensen, M. Wollbratt and K. Whålander
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 49 – No. 4/2011 (258-267)
Single-dose pharmacokinetics, pharmacodynamics and safety of AZD0837, a novel oral direct thrombin inhibitor, in young healthy male subjects
S. Johansson, M. Cullberg, U.G. Eriksson, M. Elg, K. Dunér, E. Jensen, M. Wollbratt and K. Wåhlander
AstraZeneca R&D, Mölndal, Sweden
Objective: The novel oral anticoagulant AZD0837 is currently in clinical development for the prevention of stroke and systemic embolic events in patients with atrial fibrillation. AZD0837 is bioconverted to AR-H067637, a selective and reversible direct thrombin inhibitor. This first-time-in-man study (study code D1250C00001) investigated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD0837. Methods: Healthy Caucasian male volunteers (n = 44, age 20 – 39 y) were enrolled into this study of single oral escalating doses of AZD0837 given in solution (15 – 750 mg, n = 4 per dose). PD was assessed by ex vivo measurements of activated partial thromboplastin time (APTT), ecarin coagulation time (ECT), thrombin time (TT) and thrombin generation in plasma. Results: AZD0837 was rapidly absorbed, with a mean oral bioavailability of 22 – 52%, and bioconverted to the active form, AR-H067637. In fasting subjects, maximum plasma concentrations (Cmax) for AR-H067637 occurred approximately 1 h post-dosing and declined with a mean half-life of 9.3 h. The Cmax and area under the curve for AR-H067637 showed a low to moderate inter-individual variability of 16% and 28%, respectively, and exhibited a slight deviation from dose-proportionality. AZD0837 produced a dose-dependent prolongation of APTT, ECT and TT, and decreased maximum free thrombin activity. AZD0837 was generally well tolerated. Conclusions: AZD0837 single oral doses (15 – 750 mg) are well tolerated in healthy male subjects and exhibit favorable PK properties and reproducible effects on ex vivo coagulation time variables that support further clinical development.Correspondence to:
S. Johansson
AstraZeneca R&D
Mölndal, 43183 Mölndal, Sweden
Email: Susanne.A.Johansson@astrazeneca.com
Original Research
Increase in non-transferrin bound iron and the oxidative stress status in epilepsy patients treated using valproic acid monotherapy
S. Ounjaijean, T. Westermarck, M. Partinen, E. Plonka-Poltorak, P. Kaipainen, M. Kaski, S. Fucharoen, S. Srichairatanakool and F. Atroshi
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 49 – No. 4/2011 (268-276)
Increase in non-transferrin bound iron and the oxidative stress status in epilepsy patients treated using valproic acid monotherapy
S. Ounjaijean1,2, T. Westermarck3, M. Partinen4,5, E. Plonka-Poltorak6, P. Kaipainen3, M. Kaski3, S. Fucharoen7, S. Srichairatanakool2 and F. Atroshi1
1Department of Pharmacology and Toxicology, University of Helsinki, Helsinki, Finland, 2Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, 3Rinnekoti Research Center, Espoo, 4Vitalmed Sleep Disorder Clinic and Research Center, 5Department of Clinical Neurosciences, University of Helsinki, Helsinki, Finland, 6Antiepileptic Outpatient Clinic, Provincial Hospital No 2, Rzeszow, Poland, and 7Thalassemia Research Center, Institute of Science and Technology for Research and Development, Mahidol University, Nakornprathom, Thailand
Objective: This study aims to investigate the alteration of iron homeostasis and oxidative stress status in epilepsy patients treated with valproic acid (VPA) monotherapy. Materials: 24 epilepsy patients receiving VPA monotherapy (12 men, 12 women, age 27.5 ± 7.2 y) and 24 sex- and age-matched healthy volunteers were included in the study. Methods: The level of iron status parameters; serum iron, ferritin, transferrin saturation, non-transferrin bound iron (NTBI), serum level of trace elements (copper, zinc and selenium), concentration of antioxidant parameters, activities of antioxidant enzymes and level of lipid peroxidation product were determined. Results: NTBI was found in the patients although their other iron status parameters were normal. Levels of antioxidant parameters were decreased while activities of antioxidant enzymes were increased. Levels of serum MDA were significantly increased in patients with epilepsy. The daily dose of valproic acid associated was statistically significant: serum concentration of NTBI (r = 0.579; p = 0.003) and MDA (r = 0.465; p = 0.022). A positive correlation existed between NTBI and zinc (r = 0.522; p = 0.009). Conclusion: According to our results, VPA treatment in patients with epilepsy contributes to the metabolism of iron, leading to the formation of NTBI and an increase in oxidative stress.Correspondence to:
F. Atroshi, MSc, PhD
Department of Pharmacology and Toxicology, ELTDK
P.O. Box 57, 00014, University of Helsinki, Helsinki, Finland
Email: faik.atroshi@helsinki.fi
Original Research
Antihypertensive prescribing preferences in three South Indian Hospitals: cost analysis, physicians perspectives and emerging trends
N. Sreedharan, P.G.M. Rao, N.R. Rau and P.R. Shankar
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 49 – No. 4/2011 (277-285)
Antihypertensive prescribing preferences in three South Indian Hospitals: cost analysis, physicians perspectives and emerging trends
N. Sreedharan1, P.G.M. Rao1, N.R. Rau2 and P.R. Shankar3
1Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, 2Department of Medicine, Kasturba Medical College, Manipal University, Manipal, India, and 3Department of Pharmacology, KIST Medical College, Kathmandu, Nepal
Objectives: The objectives of this study were i) to analyze the prescription pattern of antihypertensive agents in three South Indian hospitals ii) to perform cost-analysis of various antihypertensive treatment regimens iii) to examine the physicians’ perspectives of antihypertensive prescribing. Methods: A cross-sectional study was done on patients with essential hypertension (n = 2,100) by analyzing the medical records of the patients for the drugs prescribed and patient demographics. Cost comparisons were made for the most frequently prescribed agents for each class at the most frequently prescribed dose and regimen. A questionnaire was developed containing questions on familiarity with guidelines, diagnosis of clinical hypertension, an evaluation of patients and choice of drug, and was distributed to physicians in the three hospitals. Results: About one-half of the patients received monotherapy where the remaining received combination therapy for their hypertension. Calcium channel blockers (CCBs) were the most preferred agents used, either as monotherapy or combination therapy in hypertensive patients with or without comorbidities. At the most frequently prescribed dose and dosage regimen, thiazide was the least expensive antihypertensives, followed by CCBs. Physician’s responses favored the use of CCBs as first-line agent for uncontrolled hypertension and a two-drug combination approach. Conclusions: The preference of CCBs and combination-therapy over the traditionally used diuretics or beta-blockers is consistent with the outcomes of recent clinical trials that underscore the benefits of using combination therapy with CCBs as initial therapy for uncomplicated hypertension.Correspondence to:
N. Sreedharan
Department of Pharmacy Practice
Manipal College of Pharmaceutical Sciences
Manipal University
Manipal, India 576104
Email: nairsreedhar@gmail.com
Original Research
Clinical efficacy of a novel new injectable diclofenac formulation designed for intradeltoid use in post-operative pain management
P. Shah, B. Subnis, A. Varshney, C. Pradhan, T.V.S.P. Murthy, D. Shah and V. Jaiswal
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 49 – No. 4/2011 (286-290)
Clinical efficacy of a novel new injectable diclofenac formulation designed for intradeltoid use in post-operative pain management
P. Shah1, B. Subnis2, A. Varshney3, C. Pradhan4, T.V.S.P. Murthy5, D. Shah6 and V. Jaiswal7
1Department of Anaesthesia, Seth G.S. Medical college and KEM Hospital, Mumbai,
2Department of Anaesthesia, Grant Medical College and Sir J. J. Hospital, Mumbai,
3Department of Surgery, R. G. Stone Urological Research Centre, New Delhi,
4Department of Orthopaedics, Sancheti Institute for Orthopaedics and Rehabilitation
Centre, Pune, 5Department of Anaesthesia, Army Hospital Research & Referral,
New Delhi, and 6AGM and 7Vice President, Medical Services, Troikaa Pharmaceuticals
Ltd., Ahmedabad, India
Objective: A randomized study comparing efficacy and safety of a new 75 mg/1 ml formulation of injectable diclofenac sodium designed for intra-deltoid use with the conventional 75 mg/3 ml formulation given by the intra-gluteal route. Design: This was an open-label, multicentric, randomized clinical trial. Methods: A total of 250 adult patients with post-operative pain were randomized to receive either an injection diclofenac 75 mg/1 ml or diclofenac 75 mg/3 ml. Primary efficacy criteria were time to onset of analgesia and reduction in pain intensity. Severity of pain at site of injection and side effects were also evaluated. Results: 232 patients completed the study. The mean times to onset of anal-gesia were comparable (16.17 ± 12.70 min in the diclofenac 75 mg/1 ml group and 19.16 ± 11.79 min in the diclofenac 75 mg/3 ml group). However, significantly more patients achieved analgesia in less than 5 min and had less pain at the site of injection with the 1 ml formulation. The need for rescue medication was also lower with the 1 ml formulation (2.5% vs. 9.82%). No side effects were reported. A significantly larger number of patients and physicians rated the efficacy and safety of injectable diclo-fenac 75 mg/1 ml as excellent. Conclusion: Both formulations were effective and safe in the management of post-operative pain with a significantly lower need for rescue analgesia and less pain at site of injection with diclofenac 75 mg/1 ml formulation. The 1 ml formulation had an added advantage of intra-deltoid use. This would be specially helpful in obese/overweight patients with a thick subcutaneous pad of fat over the gluteal region.Correspondence to:
Dr. V. Jaiswal
Troikaa Pharmaceuticals Limited
Commerce House-1
Off Judges Bungalow Road
Ahmedabad - 380 054, India
Email: vijayajaiswal@troikaapharma.com; medicalservices@troikaapharma.com
Letter to the Editor
Highly activated oral bioavailability of tacrolimus on coadministration of oral voriconazole
Y. Inoue, T. Saito, M. Takimoto, K. Ogawa, Y. Shibuya, Y. Suzuki, M. Kato, M. Takahashi, I. Miura, Y. Hatta and J. Takeuchi
Abstract
Highly activated oral bioavailability of tacrolimus on coadministration of oral voriconazole
Y. Inoue, T. Saito, M. Takimoto, K. Ogawa, Y. Shibuya, Y. Suzuki, M. Kato, M. Takahashi, I. Miura, Y. Hatta and J. Takeuchi
