Volume 49, No. 9/2011(September)
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 Int. Journal of Clinical Pharmacology and Therapeutics
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Original Research
A survey on clinical study participation and study infrastructure at non-university hospitals in Germany
O. Heese, R.H. Böger and M. Westphal
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 49 – No. 9/2011 (531-535)
A survey on clinical study participation and study infrastructure at non-university hospitals in Germany
O. Heese1, R.H. Böger2 and M. Westphal1
1Department of Neurological Surgery, and 2Department of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Objective: In order to participate in multicenter clinical trials a fair amount of infrastructure and human resources has to be provided by hospitals. Therefore clinical trials are carried out predominantly in university hospitals. Data concerning participation in clinical trials and the infrastructure of study centers in non-university hospitals in Germany do not exist. A survey was thus conducted to evaluate the current status of clinical study performance in non-university hospitals. Materials and methods: A questionnaire comprising 10 questions covering hospital infrastructure, local study history, and the individual interest in performing studies was sent to 790 non-university hospitals in Germany. Results: 58.7% of questionnaires were returned for evaluation. 74.1% of nonuniversity hospitals participate in clinical studies. Hospital size is a significant predictor of study participation. 25.5% of hospitals have established a multidisciplinary study center. 86.2% have a certified study nurse and in 34.5% this nurse is the only person running the study center. Only 25.5% of hospitals were not interested in participating in clinical studies at all, even if an individual tailored concept were to be offered. Conclusions: The demand for more hospitals to participate in clinical trials is urgent since high quality studies are a fundamental part of clinical research. Even though 75% of non-university hospitals in Germany already participate in clinical trials, it may be possible to increase this number. In addition by establishing and developing study centers in hospitals the quality of studies will presumably rise, and due to the concentration of study resources, the number of clinical trials may increase.Correspondence to:
PD Dr. med.O. Heese
Department of Neurological Surgery
University Medical Center Hamburg-Eppendorf
Martinistraße 52
20246 Hamburg, Germany
Email: heese@uke.uni-hamburg.de
Original Research
Prescriber adherence to pharmacokinetic monitoring service recommendations for aminoglycoside dosing and the risk of acute kidney injury
S. Hennessy, C.E. Leonard, A.R. Localio, A. Cohen, W. Yang, L. Cheung, B.L. Strom, M. Herlim and H.I. Feldman
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 49 – No. 9/2011 (536-544)
Prescriber adherence to pharmacokinetic monitoring service recommendations for aminoglycoside dosing and the risk of acute kidney injury
S. Hennessy1,2,3, C.E. Leonard1,2,3, A.R. Localio1,2,3, A. Cohen1,2,3,4, W. Yang1, L. Cheung5, B.L. Strom1,2,3,6, M. Herlim1 and H.I. Feldman1,2,3,7
1Center for Clinical Epidemiology & Biostatistics, Department of Biostatistics and Epidemiology, 2Center for Education and Research on Therapeutics, 3Program for the Reduction in Medication Errors, University of Pennsylvania School of Medicine, 4Department of Health Policy & Public Health, University of the Sciences in Philadelphia, Philadelphia, PA, 5College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, 6Department of Medicine, Division of General Internal Medicine, University of Pennsylvania Health System, and 7Department of Medicine, Division of Renal Electrolyte and Hypertension Medicine, University of Pennsylvania Health System, Philadelphia, PA, USA
Objective: The importance of adherence to aminoglycoside dosing recommendations by a pharmacokinetic monitoring service for preventing acute kidney injury (AKI) is unknown. We aimed to examine the association between AKI and discordance in aminoglycoside dosing between physician orders and recommendations by a pharmacokinetic monitoring service. Materials: We utilized 2000 – 2003 data from a large quaternary care academic medical center, including: hand-written pharmacokinetic monitoring service recommendations; computerized physician order entry inpatient medication orders; and electronic inpatient laboratory orders and results. Methods: We conducted a case-control study, nested within users of intravenous aminoglycosides. Outcomes of interest were cases of AKI, as determined by changes in serum creatinine. Exposures of interest were discordances between pharmacokinetic monitoring service recommendations and physician orders in the past 2 days with regard to total daily aminoglycoside dose. Results: Most patients received once-daily or less frequent aminoglycoside dosing. In 1,414 evaluable aminoglycoside courses, 220 patients developed AKI, for a cumulative incidence of 15.6%. We identified 690 controls, matched these to 220 cases, and found adjusted odds ratios of 0.72 (95% CI: 0.37 – 1.39) for overdose discordance and of 0.83 (0.51 – 1.34) for underdose discordance, suggesting that discordance in dosing is not associated with AKI. Conclusion: Non-adherence to dosing recommendations for aminoglycosides was not associated with risk of AKI in a setting primarily of once-daily aminoglycoside administration.Correspondence to:
C.E. Leonard, PharmD
Clinical Research Pharmacist
Pharmacoepidemiology Research Fellow
826 Blockley Hall/423 Guardian Drive
Philadelphia, PA, 19104-6021 USA
Email: celeonar@mail.med.upenn.edu
Original Research
The effect of β-adrenergic blockade and COX-2 inhibition on healing of colon, muscle, and skin in rats undergoing colonic anastomosis
O. Hazut, L. Shaashua, M. Benish, B. Levi, L. Sorski, B. Benjamin, A. Hoffman, O. Zmora and S. Ben-Eliyahu
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 49 – No. 9/2011 (545-554)
The effect of β-adrenergic blockade and COX-2 inhibition on healing of colon, muscle, and skin in rats undergoing colonic anastomosis
O. Hazut1*, L. Shaashua1*, M. Benish1, B. Levi1, L. Sorski1, B. Benjamin2, A. Hoffman3, O. Zmora3 and S. Ben-Eliyahu1
1NeuroImmunology Research Unit, Department of Psychology, Tel Aviv University, 2Department of Surgery, Meir Medical Center, Tel Aviv, and 3Department of Surgery and Transplantation, Sheba Medical Center, Tel-Hashomer, Israel
Objective: COX inhibitors and β-adrenergic blockers were recently shown to reduce cancer progression in animal models through various mechanisms. These include the prevention of immune suppression during the critical perioperative period, and the preclusion of direct promoting effects of catecholamines and prostaglandins on malignant tissue growth. To assess the safety of such pharmacological treatments in the context of oncologic surgery, the current study evaluates wound healing efficacy in the skin, muscle, and colon tissues in rats undergoing colonic anastomosis. Methods: F344 rats were treated daily with a COX-2 inhibitor (etodolac), a β-adrenergic blocker (propranolol), both drugs or vehicles. All rats underwent skin punch biopsy, and half were also subjected to laparotomy and colonic anastomosis. Tensile strength of the abdominal wall and colonic bursting pressure were assessed on Days 3, 7, and 30 postoperatively, and skin biopsy site healing was scored on Days 2, 4, and 6 postoperatively. Results: None of the drug treatments produced any deleterious effects along the expected course of tissue healing. On Day 30, colon bursting pressure showed an abnormal strengthening in animals undergoing anastomosis compared to non-operated animals, across all drug treatments. This abnormal strengthening was attenuated by etodolac. In the skin, surgery reduced healing rate, irrespective of drug treatments. Conclusions: Effective doses of etodolac and propranolol caused no negative effects on wound healing processes in rats. The apparent safety of such treatments, together with their potential clinical benefits, suggests the incorporation of these treatments in oncologic patients undergoing curative tumor resection.Correspondence to:
S. Ben-Eliyahu, PhD
NeuroImmunology Research Unit
Department of Psychology
Tel Aviv University
Tel Aviv 69978, Israel
Email: shamgar@post.tau.ac.il
Original Research
Influence of common cardiac drugs on gastroesophageal reflux disease: multicenter questionnaire survey
G. Nakaji, M. Fujihara, M. Fukata, S. Yasuda, K. Odashiro, T. Maruyama and K. Akashi on Behalf of Fukuoka F-Scale Trial (FSCAT) Group
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 49 – No. 9/2011 (555-562)
Infl uence of common cardiac drugs on gastroesophageal reflux disease: multicenter questionnaire survey
G. Nakaji1, M. Fujihara1, M. Fukata1, S. Yasuda1, K. Odashiro1, T. Maruyama2 and K. Akashi1 on Behalf of Fukuoka F-Scale Trial (FSCAT) Group
1Department of Medicine and Biosystemic Science, and 2Institute of Health Science, Kyushu University, Fukuoka, Japan
Background: Although gastroesophageal reflux disease (GERD) causes noncardiac chest pain mimicking angina pectoris, systemic studies surveying the effects of common cardiac drugs on symptomatic GERD are rare. Methods: To investigate the drugrelated GERD, this multicenter trial enrolled 201 consecutive cardiac outpatients (69.7 ± 10.5 y) after obtaining written informed consent. They were assessed using the Frequency Scale for Symptoms of GERD (F-scale) to screen for GERD with a cut-off value of 8.0. Clinical background was obtained from medical records. Gastric medicine was empirically administered at the discretion of the attending physician. F-scale score and incidence of GERD were analyzed individually in relation to background and prescription. Results: The average F-scale score did not correlate with gender, age or underlying diseases. F-scale score was elevated significantly (p = 0.006) by administration of calcium channel blockers to the patients treated with gastric medicine, suggesting that calcium channel blockers exacerbate the possibly preexisting GERD. Incidence of GERD within 2 months after starting warfarin tended to be greater than that at other durations (p = 0.087). Patients showing a high score (≥ 8.0) suggestive of GERD showed a correlation with the combined administration of calcium channel blockers (OR = 3.19; 95% CI of 1.01 – 10.11; p = 0.049) and warfarin (OR = 3.05; 95% CI of 1.00 – 9.27; p = 0.049) in the best logistic model. Conclusion: Although larger cohort is required, this survey demonstrates that the combination of calcium channel blockers and warfarin is an independent risk factor for GERD.Correspondence to:
T. Maruyama, MD, PhD
Institute of Health Science
Kyushu University
Kasuga Kohen 6-1
Kasuga 816-8580, Japan
Email: maruyama@ihs.kyushu-u.ac.jp
Original Research
Pharmacokinetics and pharmacodynamics of tonapofylline in subjects with severe renal impairment and in elderly subjects
Z. Li, C. TenHoor, T. Marbury, S. Swan, Y. Zhu and B. Ticho
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 49 – No. 9/2011 (563-570)
Pharmacokinetics and pharmacodynamics of tonapofylline in subjects with severe renal impairment and in elderly subjects
Z. Li1*, C. TenHoor1**, T. Marbury2, S. Swan3, Y. Zhu1 and B. Ticho1
1Biogen Idec Inc., Cambridge, MA, 2Orlando Clinical Research Center, Orlando, FL, and 3HealthEast Care System, St. Paul, MN, USA
Objective: The study was conducted to characterize the pharmacokinetics and pharmacodynamics of tonapofylline in subjects with severe renal impairment and in elderly subjects. Method: Subjects with severe renal impairment were matched demographically with healthy subjects. Elderly subjects with normal renal function for their ages were also enrolled. All subjects (n = 8 per group) received a single intravenous administration of tonapofylline at 1 mg/kg. Results: The pharmacokinetics of tonapofylline was not significantly different in subjects with severe renal impairment, or in elderly subjects, as compared to healthy subjects. Among all pharmacokinetic parameters, the only statistically significant difference was observed for Cmax between the healthy and the severe renal impairment groups, which was 21% and considered clinically insignificant. Pharmacodynamic assessment demonstrated the natriuretic effects of tonapofylline across groups, with little accompanying kaliuresis. No change in renal function occurred after single dose of tonapofylline, despite substantial increases in excretion of urinary sodium. Single 1 mg/kg intravenous administration of tonapofylline was generally safe. Conclusion: The pharmacokinetics of tonapofylline in subjects with severe renal impairment and elderly subjects with normal renal function for age is similar to that in healthy subjects. It has been demonstrated in all groups that tonapofylline has natriuretic effects and is able to maintain renal function, which can be beneficial to patients with congestive heart failure.Correspondence to:
Dr. Z. Li
Genzyme Corporation
55 Cambridge Parkway
Cambridge, MA 02142, USA
Email: zhaoyang.li@genzyme.com
Bioavailability Section
Comparative bioavailability study of cefuroxime axetil (equivalent to 500 mg cefuroxime/tablet) tablets (Zednad® versus Zinnat®) in healthy male volunteers
Y.A. Asiri, B.M. Al-Hadiya, A.A. Kadi, K.I. Al-Khamis, H.A. Mowafy and Y.M. El-Sayed
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 49 – No. 9/2011 (571-576)
Comparative bioavailability study of cefuroxime axetil (equivalent to 500 mg cefuroxime/tablet) tablets (Zednad® versus Zinnat®) in healthy male volunteers
Y.A. Asiri1, B.M. Al-Hadiya1, A.A. Kadi2, K.I. Al-Khamis1, H.A. Mowafy3,4 and Y.M. El-Sayed3
1Department of Clinical Pharmacy, 2Department of Pharmaceutical Chemistry, 3Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, and 4Department of Pharmaceutics, College of Pharmacy, Al-Azhar University, Cairo, Egypt
This study was performed to investigate the bioequivalence of cefuroxime axetil tablets between a generic test product (A) Zednad® Tablet (500 mg cefuroxime/ tablet, Diamond Pharma, Syria), and the Reference Product (B) Zinnat® Tablet (500 mg cefuroxime/tablet, GlaxoSmithKline, Saudi Arabia). The bioavailability study was carried out for 24 healthy male volunteers. The subjects received 1 Zednad® Tablet (500 mg/ tablet) and 1 Zinnat® Tablet (500 mg/tablet) in a randomized, two-way crossover design fashion on 2 treatment days, after an overnight fast of at least 10 h, with a washout period of 7 days. 24 volunteers plus 2 alternatives completed the crossover. The bioanalysis of clinical plasma samples was accomplished by HPLC method, which was developed and validated in accordance with international guidelines. Pharmacokinetic parameters, determined by standard non-compartmental methods, and ANOVA statistics were calculated using SAS Statistical Software. The significance of a sequence effect was tested using the subjects nested in sequence as the error term. The 90% confidence intervals for the ratio between the test and reference product pharmacokinetic parameters of AUC0→t, AUC0→∞, and Cmax were calculated and found to be within the confidence limits of 80.00 – 125.00% for AUC0→t, AUC0→∞ and Cmax. The study demonstrated that the test product (A) was found bioequivalent to the reference product (B) following an oral dose of 500 mg tablet. Therefore, the two formulations were considered to be bioequivalent.Correspondence to:
H.A. Mowafy, PhD
Department of Pharmaceutics
College of Pharmacy
King Saud University
P.O. Box 2457
Riyadh 11451, Saudi Arabia
Email: hamam671@yahoo.com
