Doses required to achieve desired vancomycin concentrations are similar in morbidly obese and normal weight patients when TBW is used as a dosing weight for the obese (approximately 30 mg x kg(-1) x d(-1)). Shorter dosage intervals may be needed when dosing morbidly obese patients so that steady-state trough concentrations remain above 5 microg x ml(-1) in this population. Because of the large amount of variation in required doses, vancomycin serum concentrations should be obtained in morbidly obese patients to ensure that adequate doses are being administered. Dosage requirements for morbidly obese patients with renal dysfunction require further study.

Ten healthy adults participated in a randomized, crossover drug interaction study testing procainamide only, procainamide plus levofloxacin, and procainamide plus ciprofloxacin. During levofloxacin therapy, most procainamide and N-acetylprocainamide (NAPA) pharmacokinetic parameters, including decreased renal clearances and renal clearance/creatinine clearance ratios, changed (P < 0.05). During ciprofloxacin treatment, only procainamide and NAPA renal clearances decreased significantly.Renal drug interactions in patients are often overlooked when new drug therapy is added to existing therapeutic regimens. Procainamide, N-acetylprocainamide (NAPA; the active metabolite of procainamide), and several fluoroquinolone antibiotics are eliminated renally by active tubular secretion (9,11,15,16,21). Procainamide serum concentrations increase and its pharmacokinetics change due to concurrent therapy with ofloxacin (15). The purpose of this study was to investigate the possibility of a renal drug interaction between procainamide and levofloxacin, one of the stereoisomers of ofloxacin. For comparison, the potential for a ciprofloxacin-procainamide drug interaction was also studied.(A portion of this work was presented in abstract form at the 2001 American College of Clinical Pharmacology Annual Meeting, Tampa, Fla.)Ten healthy adults (five males, five females; ages, 21 to 35 years; weights, 52 to 87 kg; seven Caucasians, three Asians) participated in the study. The investigation was approved by the university human subjects committee, and subjects provided written informed consent. All individuals had normal physical examinations, laboratory screening tests (serum electrolytes, renal and liver function tests, and complete blood cell counts), and 12-lead electrocardiograms. Subjects were within 20% of their ideal body weight, did not smoke tobacco-containing products, had no known allergy to study medications, took no additional medications, and, if female, had negative serum pregnancy tests (6). Beverages containing alcohol or methylxanthines were not allowed during the study period.The study was a three-way randomized, controlled trial designed to investigate a potential drug interaction between procainamide and two fluoroquinolone antibiotics. Subjects were not blinded from antibiotic study drugs because of obvious differences in dosage forms and administration schedules. Each of the following procedures was performed with procainamide alone (control phase) or on the fifth day of fluoroquinolone oral administration (500 mg of levofloxacin every day at 0800 h and 500 mg of ciprofloxacin every 12 h at 0800 h and 2000 h). Prior to admission to the Clinical Research Center for administration of procainamide, subjects were allowed to selfadminister the fluoroquinolone at home; compliance was assured by inspection of a medication administration diary, tablet counts of doses remaining in the pill vial, and subject interviews by investigators. In order for the study to proceed, all drug doses needed to be administered within 15 ...

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The objective of this study was to assess the pharmacokinetics of diclofenac sodium and its five metabolites following administration of a 150 mg oral dose to healthy subjects and patients with either chronic active hepatitis of varying morphology or alcoholic cirrhosis. Six healthy subjects, 6 chronic active hepatitis patients, and 6 alcoholic cirrhosis patients were enrolled in this prospective, open-label, parallel study. Blood samples were drawn at 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, 24, 48, 72, 144, 312, and 480 hours, and urine samples were collected for 144 hours after administration of a single oral dose of diclofenac sodium. The mean area under the serum concentration-time curve extrapolated to infinity, oral clearance, half-life, maximal concentration, and time to peak concentration for diclofenac and its metabolites were determined and compared using analysis of variance. Cirrhotics had a mean +/- SD diclofenac AUC value (19,114 +/- 6806 ng.h/ml) significantly different (p < 0.02) from hepatitis patients (6071 +/- 1867 ng.h/ml) and healthy subjects (7008 +/- 2006 ng.h/ml), whereas healthy subjects and hepatitis patients had similar values. Comparable results were found for 4'-hydroxydiclofenac. The AUC values for 3'-hydroxydiclofenac and 3'-hydroxy-4'methoxydiclofeanc were significantly different when healthy subjects were compared to cirrhotics. However, hepatitis subjects were not significantly different from either group. The results indicate that hepatitis does not alter the pharmacokinetics of diclofenac. Alcoholic cirrhosis increased the mean diclofenac AUC approximately three times compared to normal subjects, indicating that one-third of the usual dose in cirrhotics would produce equivalent AUC values in normal subjects and subjects with alcoholic cirrhosis. However, since pharmacodynamic measurements were not made and no increase in untoward or side effects was noted in the alcoholic cirrhosis patients after a single dose, maintenance doses should be titrated to patients response.

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