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The pharmacokinetic parameters of lidocaine are pertinent to the determination of both appropriate loading doses and constant infusion rates that achieve a therapeutic plasma concentration while avoiding toxicity. Because lidocaine is used primarily in older patients who may have concurrent diseases, the effects of disease states on lidocaine disposition are important when calculating lidocaine doses. Patients with congestive heart failure and hepatic disease have pronounced changes in lidocaine clearance. Patients placed on prolonged lidocaine infusions have a change in disposition half-life of the drug. Patients with renal disease do not have significant alterations in handling the parent compound but, because of the dependence of glycinexylidide elimination on renal function, may accumulate the metabolite and develop central nervous system toxicity. Even though there are differences in some of the pharmacokinetic variables for lidocaine in young and elderly patients, the clearance of the drug was not significantly different in the two patient groups. The effects of concurrently administered drugs on lidocaine pharmacokinetics remain to be more widely studied in patients.

Furosemide solution was orally administered to 21 healthy adult males to determine dose proportionality over the dose range used and the reproducibility of disposition following a repeated dose. Furosemide solution was given in doses of 20, 40, and 80 mg, with the 40 mg dose repeated once. Blood was collected for 12 hours post-dose and urine for 24 hours. The maximum plasma concentrations resulting from 20, 40, and 80 mg doses were significantly different (p less than 0.05). Dose normalized maximum concentrations for the 20 and 80 mg doses were significantly different (p less than 0.05). Mean time to Cpmax was 50 minutes, with no differences observed among doses. Plasma AUCs were significantly different (p less than 0.05) for 20, 40, and 80 mg. Dose normalized AUCs were not significantly different. Mean amounts of furosemide in urine (Xu) were 9.62, 16.7, and 32.0 mg for the 20, 40, and 80 mg doses, respectively. These amounts were significantly different (p less than 0.05); dose normalized amounts were not significantly different. Renal clearances of furosemide following the three doses were not significantly different. Regressions of Cpmax, AUC and Xu on dose were significant. There were no significant differences in Cpmax, tmax, AUC or Xu for 40 mg given on two separate days. Renal clearance of furosemide was statistically different for 40 mg given on two separate days, but the difference was not clinically significant. The pharmacokinetics of furosemide are linear over the dosage range studied. Furosemide 40 mg given on two separate days results in similar disposition parameters.