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The clearances of inulin and gentamicin were studied before and after intravenous furosemide in seven patients. There was a significant fall in glomerular filtration rate after furosemide and a similar though less marked fall in gentamicin clearance in six of the seven subjects. Small but consistent increases in plasma gentamicin concentrations were observed after furosemide. The reduction in clearance may explain the enhanced risk of nephrotoxicity in patients receiving both aminoglycosides and diuretics. [ABSTRACT FROM AUTHOR]

A patient is described in whom there was strong circumstantial evidence of an interaction between warfarin and co-trimaxazole. To test the validity of this hypothesis a series of in vitro and in vivo human studies were untaken. The results indicate that interaction may occur in which the sulphamethoxazole moiety of co-trimoxazole displaces warfarin from its binding sites on plasma albumin. Nevertheless, this interaction occurs only at high plasma levels of warfarin and is most likely to be clinically significant only in patients receiving high doses of warfarin who have low plasma albumin concentrations. These studies indicate that the use of co-trimoxazole is not contra-indicated in patients receiving warfarin therapy, but care should be exercised, especially in patients with high plasma warfarin:albumin ratios. [ABSTRACT FROM PUBLISHER]

Furosemide kinetics were studied in normal volunteers and patients with renal failure. Comparison of results from intravenous bolus and intravenous infusion in normal subjects showed no significant model dependency of estimations of furosemide clearance, although the average clearance by fitting to a one-compartment model was 16% higher than that obtained by fitting to a two-compartment model. Normal subjects had a total body clearance of furosemide of 1.53 +/- 0.11 (SE) ml/min/kg, a volume of the central compartment of 2.61 +/- 0.37 L, a volume of the peripheral compartment of 2.48 +/- 0.24 L, and a half-life of 0.8 +/- 0.06 hr and they absorbed 68.9% +/- 7.1% of a solution of furosemide given by mouth. The corresponding values in patients with renal failure were 0.27 +/- 0.03 ml/min/kg, 8.02 +/- 0.96 L, 14.1 +/- 3.57 L, 14.2 +/- 2.30 hr, and 43.4% +/- 8.0%, all differing significantly different from the normal. The bioavailability of 500-mg tablets of furosemide in the renal failure patients was 43.4% +/- 7.4%, equivalent to the absorption of the dose given to the same patients in the form of a solution.

Phenelzine cannot be extracted as such from biological fluids. Formation of the acetonide derivative prior to extraction allows phenelzine to be extracted and assayed by gas chromatography at levels down to 0.5 microg/ml. At this sensitivity the drug can be detected in urine but not in plasma, after therapeutic doses. Persons typed as slow acetylators of sulphadimidine excreted approximately twice as much unmetabolized phenelzine in urine compared to fast acetylators.

The pharmacokinetics of procainamide was determined in 21 lidocaine-resistant patients who received the drug according to a pharmacokinetically designed double-infusion technique. Thirteen patients were phenotyped as slow acetylators, seven as fast, and one as intermediate. The total body clearances (ClT) of PA in slow and fast acetylators were 22.6 and 34.8 liters/hr, respectively. The fraction of PA cleared by the formation of NAPA in the corresponding acetylator group was 0.2 and 0.4. Renal impairment affected the pharmacokinetics of PA more profoundly as the ClT's of PA in patients with and without renal impairment were 17.9 and 31.2 liters/hr, respectively. None of the calculated volumes of distribution was affected by acetylator phenotype or renal impairment. These data identify the contribution of at least two of the major factors accounting for variability in PA disposition in patients undergoing therapy.

Adriamycin adsorption to four sorbents, uncoated activated charcoal, acrylic hydrogel-coated activated charcoal, a polystyrene non-ionic resin, and a pyrolized resin, was determined in vitro in aqueous and plasma solutions. Uncoated charcoal and pyrolized resin were most efficient in removing Adriamycin from these solutions. Four hours after an iv bolus of Adriamycin (2.5 mg/kg) to beagle dogs, acrylic hydrogel-coated activated charcoal hemoperfusion was performed. Extraction of Adriamycin averaged 43% throughout the 3-hour hemoperfusion period and resulted in a 20-fold increase in total body elimination of Adriamycin but plasma drug concentrations returned towards control values following hemoperfusion. Pharmacokinetic analysis of plasma Adriamycin profiles suggested that reduction of tissue concentrations of Adriamycin could be attained if hemoperfusion periods were extended. It is suggested that hemoperfusion may be useful in reducing blood levels of Adriamycin in patients with hepatic disease or accidental overdosage, but that reduction of tissue levels of Adriamycin would require extended or repeated hemoperfusion treatments.

The presence and mechanism of synergism of action between ethanol and amylobarbitone, phenobarbitone or methaqualone was determined by application of simple pharmacokinetic models to log dose-response curves and plasma concentration-time curves for the hypnotics alone or when ethanol was given concurrently. For all three hypnotics, ethanol was found to increase the duration of hypnosis, but the mechanism of action was different for each. A sub-hypnotic dose of ethanol increased the volume of distribution of amylobarbitone and the consequent reduction in fractional elimination prolonged the half-life of the hypnotic. The distribution and elimination of methaqualone were not affected by ethanol, but there was a sensitisation of the target organ, shown by a reduced minimum effective dose. The minimum effective dose of phenobarbitone was also reduced by ethanol, but in addition, the rate of elimination of phenobarbitone was increased after the period of hypnosis.

Slow-release procainamide given 8-hourly is shown to produce plasma levels generally accepted as giving effective prophylaxis against ventricular dysrhythmias occurring after recent myocardial infarction. Patients can be classified into 'slow' and 'fast' acetylators of procainamide. Knowledge of acetylator status is helpful in determining the dose of procainamide necessary to attain effective steady-state plasma levels while avoiding toxic ones. Acetylator status cannot be assessed accurately using sulphadimidine when the patients are also taking procainamide.