European journal of clinical pharmacology
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The pharmacokinetics and pharmacodynamics of pancuronium were studied following intravenous infusion in eleven patients undergoing surgical anaesthesia. Measurement of the plasma concentrations (Cp) of the neuromuscular blocking agent ( NMBA ) and the concomitant intensities of paralysis allowed their simultaneous modelling. The pharmacokinetic parameters derived for pancuronium were in the range of previously reported values, except that the mean total systemic plasma clearance (0.79 +/- 0.28 ml X min-1 X kg-1) was reduced and the mean terminal phase half-life (169 min) was longer in these patients. ⋯ Using this latter approach, the ECp50 estimated during onset of paralysis was significantly higher than that estimated during offset of paralysis (p less than 0.05); no such difference was apparent between this latter parameter and the ECpss (50) of the integrated effect model (p greater than 0.05). No significant differences were observed between any of the pharmacodynamic parameter estimates generated from the data obtained from the two methods of assessment of neuromuscular function (mechanical vs. EMG response) (p greater than 0.05).
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Eur. J. Clin. Pharmacol. · Jan 1983
Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients.
Aminoglycoside pharmacokinetics were determined in 30 normal weight patients and 30 morbidly obese patients (greater than 90% overweight). All had normal renal function and a gram-negative infection (documented by cultures, fever and elevated white blood cell counts) which was treated only with aminoglycoside antibiotics. The normal weight and morbidly obese patients were matched with respect to the following criterion: age, sex, ideal body weight (IBW), serum creatinine, site of infection, and type of aminoglycoside antibiotic (gentamicin, tobramycin, or amikacin). ⋯ Average half-life was 2 h for both the morbidly obese and normal weight patients. The mean volumes of distribution and clearances were significantly larger in the morbidly obese (23.3 l and 135.8 ml/min for gentamicin, 29.9 l and 162.4 ml/min for tobramycin, and 26.8 l and 157.3 ml/min for amikacin) than in normal weight patients (17.0 l and 95.9 ml/min for gentamicin, 18.3 l and 101.3 ml/min for tobramycin, and 18.6 l and 99.2 ml/min for amikacin). As a result of altered aminoglycoside pharmacokinetics, morbidly obese patients required significantly larger mean doses (540 mg/d for gentamicin, 690 mg/d for tobramycin and 1970 mg/d for amikacin) when compared to the normal weight patients (380 mg/d, 420 mg/d and 1420 mg/d, respectively; p less than 0.005) in order to achieve comparable serum concentrations.
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Eur. J. Clin. Pharmacol. · Jan 1983
Comparative StudyInfluence of age on amikacin pharmacokinetics in patients without renal disease. Comparison with gentamicin and tobramycin.
The influence of age on amikacin pharmacokinetics was examined in 87 patients with normal renal function. All patients had a gram negative infection, were febrile, weighed within 20% of their ideal body weight, did not receive penicillin antibiotics concurrently, had normal hematocrits and had a measured 24 h creatinine clearance greater than 80 ml/min/1.73 m2. 31 patients were 20-39 years old, 27 patients were between the ages of 40-59 years, and 29 patients were 60-79 years old. These patients were compared to patients in similar previous studies who received gentamicin or tobramycin. ⋯ Patients over 40 years old tended to be underdosed with amikacin and the other 2 aminoglycosides. The average amikacin dose needed to achieve the desired steady-state concentrations was 18.9 mg/kg/day. 52% of the amikacin patients required doses greater than the recommended maximum (15 mg/kg/day). Since aminoglycoside pharmacokinetics do not change as age increases, doses do not need to be arbitrarily changed in older patients with normal renal function.
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Pancuronium in bolus doses of 40 to 350 microgram/kg was administered to surgical patients in order to evaluate the linearity of its pharmacokinetics. The profile of the plasma decay curve and of its urinary elimination were compared with reference to the administered dose. It was possible to superimpose the dose-normalized plasma decay-curves. ⋯ The profiles of cumulative urinary excretion were also dose-independent. After 6 and 24 h, 57% and 69% of the administered dose, respectively, had been excreted in the urine. The results indicate that the pharmacokinetics of pancuronium is linear.
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Eur. J. Clin. Pharmacol. · Oct 1982
Randomized Controlled Trial Clinical TrialParacetamol plus supplementary doses of codeine. An analgesic study of repeated doses.
A double-blind, multicentre analgesic trial was carried out in patients suffering from pain after removal of an impacted lower wisdom tooth. 266 patients were evaluated after random allocation to treatment with paracetamol 500 mg, paracetamol 500 mg plus codeine 20 mg, paracetamol 500 mg plus codeine 30 mg, or paracetamol 500 mg plus codeine 40 mg. On the day of surgery the patients assessed their own pain intensity hourly on a visual analogue scale. ⋯ In the comparison of side effects, their frequency increased with increasing amounts of codeine. In clinical practice codeine 30 mg appeared to be the optimal supplement for paracetamol 500 mg.