Basic & clinical pharmacology & toxicology
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Basic Clin. Pharmacol. Toxicol. · Dec 2012
Randomized Controlled TrialThe absorption profile of pregabalin in chronic pancreatitis.
It was recently shown that pregabalin decreased pain associated with chronic pancreatitis. It is well known that pancreatitis patients suffer from fat malabsorption with accompanying diarrhoea because of loss of exocrine pancreatic enzyme production. This may lead to changes in the mucosal surface in the small intestine and possibly affect the absorption of pregabalin. ⋯ Time to maximum observed plasma concentration (T(max) ) was 1.53 (95% CI 1.09-2.05). The maximum plasma concentration (C(max) ) was 1.98 μg/ml (95% CI 1.69-2.34), and area under the plasma concentration-time profile (area under the curve) was 18.2 μg*hr/ml (95% CI 14.7-26.3). Pregabalin is well absorbed in patients with chronic pancreatitis, and the pharmacokinetic profile of pregabalin is not extensively affected by chronic pancreatitis.
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Basic Clin. Pharmacol. Toxicol. · Dec 2012
Randomized Controlled TrialThe analgesic concentration of oxycodone with co-administration of paracetamol -- a dose-finding study in adult patients undergoing laparoscopic cholecystectomy.
We have previously shown that paracetamol has an opioid-sparing effect in tonsillectomy, and now, we evaluated the analgesic efficacy of paracetamol i.v. in early post-operative pain after laparoscopic cholecystectomy (LCC). Twenty-four patients with LCC were randomized to receive paracetamol i.v. 1 g (group 1) or 2 g (group 2) at the end of surgery. All patients were provided 0.1 mg/kg of oxycodone i.v. 15 min. before the end of surgery. ⋯ At the onset of pain, P-oxycodone (MEC) was similar in both groups, 25 ng/ml (19-32) in group 1 and 24 ng/ml (16-34) in group 2. The pain relief (MEAC) was achieved in group 1 with P-oxycodone 70 ng/ml (30-131) and in group 2 with 62 ng/ml (36-100) (p = 0.48). In conclusion, in the early-phase after LCC, there was no significant difference between the effect of paracetamol doses of 1 g and 2 g i.v. on the need of i.v. oxycodone.
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Basic Clin. Pharmacol. Toxicol. · Nov 2012
Randomized Controlled Trial Comparative Study Clinical TrialRifampicin has a profound effect on the pharmacokinetics of oral S-ketamine and less on intravenous S-ketamine.
Low-dose ketamine is currently used in several acute and chronic pain conditions as an analgesic. Ketamine undergoes extensive metabolism and is thus susceptible to drug-drug interactions. We examined the effect rifampicin, a well-known inducer of many cytochrome P450 (CYP) enzymes and transporters, on the pharmacokinetics of intravenous and oral S-ketamine in healthy volunteers. ⋯ Rifampicin decreased greatly the peak plasma concentration of oral S-ketamine by 81% (p < 0.001), but shortened only moderately the elimination half-life of intravenous and oral S-ketamine. Rifampicin decreased the ratio of norketamine AUC (0-∞) to ketamine AUC (0-∞) after intravenous S-ketamine by 66%, (p < 0.001) but increased the ratio by 147% (p < 0.001) after the oral administration of S-ketamine. Rifampicin profoundly reduces the plasma concentrations of ketamine and norketamine after oral administration of S-ketamine, by inducing mainly its first-pass metabolism.
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Basic Clin. Pharmacol. Toxicol. · Jun 2012
Randomized Controlled TrialAssessment of the analgesic effect of remifentanil using three pain models in healthy Korean volunteers: a randomized, controlled study.
Quantitative pain assessment in human beings is useful for developing new analgesics. This study assessed the analgesic effect of remifentanil in 20 healthy Korean men using three pain models to investigate whether these models can be used in Asians. The study was a double-blind, placebo-controlled, two-way cross-over study. ⋯ Remifentanil conferred a significantly higher pressure pain threshold and tolerance than placebo (p = 0.0001). There was a trend of increasing mechanical pain threshold with remifentanil, although it was not statistically significant. The results suggest that heat pain and pressure pain models are valid in East Asians for assessing analgesic effects.
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Basic Clin. Pharmacol. Toxicol. · May 2012
Randomized Controlled TrialLoading dose required to achieve rapid therapeutic teicoplanin trough plasma concentration in patients with multidrug-resistant gram-positive infections.
Teicoplanin is an antibiotic drug prescribed for the treatment of multidrug-resistant Gram-positive infections. However, there is currently no consensus as to the optimal teicoplanin loading dose. The objective of this study was to compare plasma concentrations of teicoplanin in patients with multidrug-resistant Gram-positive infections after the administration of two different loading doses. ⋯ In addition, more patients in group B achieved therapeutic concentrations from days 2 through 12. In conclusion, despite limitations in drawing definitive conclusions because of a relatively small sample size and variability in renal impairment among patients, our findings suggest that a teicoplanin loading dose of 12 mg/kg body-weight results in a safe and rapid attainment of therapeutic trough plasma concentrations. This regimen may enhance treatment efficacy.