Methods and findings in experimental and clinical pharmacology
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Methods Find Exp Clin Pharmacol · Sep 2006
Randomized Controlled TrialThe effect of CYP2C19 substrate on the metabolism of melatonin in the elderly: A randomized, double-blind, placebo-controlled study.
The metabolism of melatonin to 6-sulphatoxymelatonin (aMT6S) and N-acetylserotonin (NAS) is catalyzed by cytochrome-P450 (CYP) isozymes CYP1A2 and CYP2C19 respectively. We studied the in vivo effect of CYP2C19 substrate (citalopram, omepratzole, or lansopratzole) on the metabolism of endogenous and exogenous melatonin by measuring the excretion of urinary aMT6S, the main metabolite of melatonin, and a reliable estimate of plasma melatonin in 15 insomniac psychogeriatric inpatients. The effect of melatonin treatment on sleep parameters was also assessed. ⋯ The sleep parameters in the patients on melatonin treatment did not differ from those in the patients treated with placebo. In conclusion, it may be inferred that CYP2C19 substrate slows the metabolism of exogenous melatonin and increases its bioavailability, as shown by the augmented excretion of aMT6S, probably by inhibiting the conversion of melatonin to NAS via CYP2C19 isozyme. Melatonin therapy may not affect the sleep parameters in our psychogeriatric inpatients.
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Methods Find Exp Clin Pharmacol · Sep 2005
Randomized Controlled TrialEffects of granisetron with droperidol or dexamethasone on prevention of postoperative nausea and vomiting after general anesthesia for cesarean section.
This prospective, placebo-controlled, double-blinded, and randomized study was undertaken to compare the efficacy of granisetron, droperidol, and combinations of granisetron with droperidol or dexamethasone on postoperative nausea and vomiting in patients undergoing general anesthesia for cesarean section. Patients (n = 150) who were scheduled for cesarean section under general anesthesia were randomly assigned to one of the five groups: physiological saline 5 ml in Group A, granisetron 40 microg/kg + dexamethasone 8 mg in Group B, granisetron 40 microg/kg + droperidol 1.25 mg in Group C, droperidol 1.25 mg in Group D, and granisetron 40 microg/kg in Group E were administered intravenously after clamping of the fetal umbilical cord. Postoperative nausea and vomiting was observed for 024 h after the anesthesia. ⋯ All granisetron groups were more effective than placebo and droperidol groups during the postoperative 3-24 h (p < 0.01). Although this trial lacks statistical power, granisetron alone and combinations with droperidol or dexamethasone were effective similarly. All treatment groups, except droperidol during the postoperative 3-24 h, were effective for prevention of postoperative nausea and vomiting during the postoperative 0-24 h.
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Methods Find Exp Clin Pharmacol · Jul 2005
Randomized Controlled Trial Comparative StudyPharmacodynamic study of procaterol hydrochloride dry powder inhaler: evaluation of pharmacodynamic equivalence between procaterol hydrochloride dry powder inhaler and procaterol hydrochloride metered-dose inhaler in asthma patients in a randomized, double-dummy, double-blind crossover manner.
Therapeutic equivalence between procaterol hydrochloride dry powder inhaler (Meptin DPI) and procaterol hydrochloride metered-dose inhaler (Meptin MDI), the currently marketed formulation, was assessed in 16 patients with bronchial asthma. The study was conducted in a randomized, double-dummy, double-blind crossover manner, using forced expiratory volume in the first second (FEV1) as an index of bronchodilatory effect. In Period I, the patients received 20 mcg of either Meptin DPI or Meptin MDI, and then crossed over in Period II after a washout interval of 3--28 days. ⋯ Factors used for the analysis were the treatment group and/or carryover effect, patients within each group, period, and treatment. The 90% confidence intervals for the differences between the two treatments were --0.0995 to --0.0204 (L) for mean AUC (FEV1)/h and --0.102 to --0.022 (L) for mean peak FEV1, both within the acceptance criteria of --0.15 to 0.15 (L). Meptin DPI was therefore assessed as being equivalent to the current Meptin MDI.
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Methods Find Exp Clin Pharmacol · Jan 2005
Randomized Controlled Trial Clinical TrialPharmacodynamic effects of 3-day intravenous treatment with pantoprazole or ranitidine after 10 days of oral ranitidine.
Tachyphylaxis (drug tolerance) is an undesirable condition in drug therapy with histamine-2-receptor antagonists (H2RAs). The concept of overcoming tachyphylaxsis via intravenous (i.v.) administration of proton-pump inhibitors (PPIs) or H2RAs is of significant interest to physicians. In the present study, 32 healthy Helicobacter pylori negative male volunteers were evaluated for the ability of i.v. pantoprazole or i.v. ranitidine to overcome oral ranitidine tachyphylaxis. ⋯ After 10 days of oral ranitidine treatment, tachyphylaxis was present in all volunteers. Within 1 day of continuous i.v. pantoprazole or i.v. ranitidine administration, 24-h median gastric pH increased from pH 1.45 to pH 3.50 (241%) and from pH 1.50 to pH 2.35 (157%), respectively. I.v. pantoprazole was found to be significantly more effective (p<0.05) than i.v. ranitidine in increasing the 24-h gastric pH after oral ranitidine tachyphylaxis.
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Methods Find Exp Clin Pharmacol · Sep 2003
Randomized Controlled Trial Comparative Study Clinical TrialBioavailability of two new formulations of paracetamol, compared with three marketed formulations, in healthy volunteers.
The aim of this study was to compare the main pharmacokinetic characteristics of two new paracetamol formulations, powder sachet and tablet, with that of three commercially available paracetamol formulations: two conventional solid tablets and one effervescent tablet. Twelve healthy volunteers participated in an open, single dose (paracetamol 1,000 mg), randomized, five-way, crossover study. Formulations studied included: formulation A: 2 x 500 mg paracetamol tablets (Laboratorios Belmac S. ⋯ Formulations A, B and E showed significantly shorter tmax than formulation C. The tmax and Cmax values found for formulations A and B were very similar to that found for E, an effervescent tablet formulation. In conclusion, the two new formulations of paracetamol tested in this study were absorbed rapidly after a single oral dose in healthy volunteers, similar to an effervescent paracetamol formulation and significantly faster than two ordinary commercialized paracetamol tablets.