British journal of clinical pharmacology
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Br J Clin Pharmacol · Jun 2001
Randomized Controlled Trial Comparative Study Clinical TrialSimultaneous administration of a cocktail of markers to measure renal drug elimination pathways: absence of a pharmacokinetic interaction between fluconazole and sinistrin, p-aminohippuric acid and pindolol.
Previous studies suggest that estimated creatinine clearance, the conventional measure of renal function, does not adequately reflect changes in renal drug handling in some patients, including the immunosuppressed. The aim of this study was to develop and validate a cocktail of markers, to be given in a single administration, capable of detecting alterations in the renal elimination pathways of glomerular filtration, tubular secretion and tubular reabsorption. ⋯ This study found no interaction between markers and fluconazole in healthy male subjects, suggesting that a single administration of this cocktail of markers of different renal processes can be used to simultaneously investigate pathways of renal drug elimination.
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Br J Clin Pharmacol · Apr 2001
Randomized Controlled Trial Clinical TrialA dose-response study of adrenaline combined with lignocaine 2%: effect on acute postoperative pain after oral soft tissue surgery.
The combination of lignocaine and adrenaline may cause more postoperative pain than other types of local anaesthetic agents with comparable clinical efficacy. This study investigates the dose-response effect of adrenaline added to lignocaine on postoperative pain, when used as local anaesthetic for oral soft tissue surgery. ⋯ High adrenaline concentrations (1 : 80 000) combined with lignocaine local anaesthetic solution offers no advantage with respect to pain alleviation during the immediate postoperative pain period. High exogenous adrenaline concentrations may play a significant role in enhancing acute postoperative intensity.
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Br J Clin Pharmacol · Apr 2001
Randomized Controlled Trial Clinical TrialLack of effect of ondansetron on the pharmacokinetics and analgesic effects of morphine and metabolites after single-dose morphine administration in healthy volunteers.
The purpose of this investigation was to study the influence of ondansetron on the single-dose pharmacokinetics and the analgesic effects elicited by morphine and the 3- and 6-glucuronide metabolites of morphine in healthy volunteers. ⋯ The results of this study suggest that administration of ondansetron (16 mg i.v.) does not alter the pharmacokinetics of morphine and its 3- or 6-glucuronide metabolites to a clinically significant extent, nor does it affect the overall analgesic response to morphine as measured by the contact thermode system.
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Br J Clin Pharmacol · Oct 2000
Randomized Controlled Trial Clinical TrialA double-blind, placebo-controlled study to assess tolerability, pharmacokinetics and preliminary pharmacodynamics of single escalating doses of Z13752A, a novel dual inhibitor of the metalloproteases ACE and NEP, in healthy volunteers.
The objective of this study was to evaluate the tolerability of a novel dual ACE-NEP inhibitor, Z13752A, after the oral administration of rising single doses in healthy volunteers. This study was also a preliminarily investigation of Z13752A pharmacodynamics (PD) and pharmacokinetics (PK). ⋯ Z13752A showed a good single dose tolerability profile at doses up to 800 mg. The pharmacokinetic data indicate that Z13752A administered orally is rapidly absorbed and available to the systemic circulation in humans. The relatively slow clearance indicates that a once-a-day dose regimen could be considered for Z13752A.
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Br J Clin Pharmacol · Sep 2000
Randomized Controlled Trial Clinical TrialEffect of P-glycoprotein modulation on the clinical pharmacokinetics and adverse effects of morphine.
To investigate the effect of acute P-glycoprotein inhibition by the multidrug-resistance (MDR) modulator valspodar (SDZ PSC 833; PSC) on the pharmacokinetics, and potentially adverse pharmacodynamic effects of morphine, and its principal pharmacologically active metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). ⋯ Acute inhibition of P-glycoprotein by PSC in this setting does not affect the pharmacokinetic or safety-related pharmacodynamic profile of morphine in a clinically significant manner.