Lorcainide kinetics and protein binding in patients with end-stage renal disease.

Lorcainide is a new antiarrhythmic drug undergoing clinical investigation for management of patients with ventricular arrhythmias. In this study we investigated the kinetic profile of lorcainide in nine patients with end-stage renal disease. A single intravenous bolus of 100 mg of the drug was injected while the patients were undergoing hemodialysis or during the off-dialysis period. Renal disease did not alter the kinetic properties of lorcainide; the elimination t1/2 beta during hemodialysis was 8.61 +/- 6.35 h, not significantly different from 7.04 +/- 4.12 h off-dialysis. Serum protein binding of lorcainide was investigated in vitro, and the percent binding of lorcainide to serum proteins of normal volunteers and renal or cardiac patients was not significantly different. These data suggest that renal disease should not alter either the dose or the dosing interval of lorcainide.

Unidirectional absorption of gentamicin from the peritoneum during continuous ambulatory peritoneal dialysis.

Gentamicin kinetics were determined after intravenous or intraperitoneal injection in five patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Our objective was to determine rate of absorption of gentamicin from the peritoneum into the systemic circulation and vice versa. After intraperitoneal instillation of 1 mg/kg in the CAPD fluid during a 6-hr dwell time, the antibiotic appeared in the serum within 15 min in four of five patients. Peak serum concentrations ranged between 1.6 and 7.2 mg/l(mean +/- SD = 3.52 +/- 2.22) in all five patients and the time to reach peak concentration was 3.8 +/- 1.5 hr. Peritoneal gentamicin clearance was 13 ml/min. Percent extraction of gentamicin from the PD fluid within the 6 hr of intraperitoneal exposure ranged from 65% to 100% (mean +/- SD = 86.8 +/- 13.2). The fraction of the intraperitoneal dose absorbed into systemic circulation was found to be 0.84 independently by calculating the ratio of AUCip and AUCiv. When the same dose of gentamicin was injected intravenously (1 mg/kg), no gentamicin could be detected in the peritoneal fluid in three of five patients and only a very small amount of the drug was present for a brief period of time in the remaining two. The kinetic parameters of intravenous gentamicin were: volume of distribution, 0.3 l/kg; elimination rate constant, 0.028 hr(-1), plasma clearance 0.009 l/kg . min(-1), and half-life 27.4 hr. In two patients with acute peritonitis treated with intraperitoneal gentamicin, peak serum concentrations were found to range between 3.5 and 4.5 mg/l. These data suggest that gentamicin is rapidly absorbed from the peritoneal fluid into the blood compartment, but that occurrence of the reverse exchange is negligible. Thus, CAPD would not be expected to alter the elimination characteristics of intravenous gentamicin. Instillation of gentamicin in CAPD fluid may allow rapid absorption to reach therapeutic serum concentrations.

An unusual case of tinea versicolor in an immunosuppressed patient.

A most unusual case of tinea versicolor is presented in which the eruption was localized only to the patient's flexural areas. This is an additional case of tinea versicolor appearing in a renal transplant patient undergoing immunosuppressant therapy. The role that immunosuppressive agents may have played in this case is also presented.

Indomethacin-induced prostaglandin inhibition with hyperkalemia. A reversible cause of hyporeninemic hypoaldosteronism.

Hyporeninemic hypoaldosteronism was diagnosed in a young woman with glomerulonephritis who was receiving indomethacin therapy. Despite only mildly abnormal renal function, serum K+ was elevated to 6.2 meq/L, and plasma renin activity (0.12 ng/mL h) and aldosterone (4.4 ng/dL) failed to respond to the combined stimuli of furosemide and posture. Urinary prostaglandin E2 (PGE2) was suppressed (70 ng/24 h). When indomethacin was withdrawn, significant kaliuresis occurred, accompanied by normalization of serum K+ and PGE2 and a supranormal rebound in renin and aldosterone levels. Challenge with indomethacin resulted in antikaliuresis and resuppression of PGE2, renin, and aldosterone. This case study documents for the first time that indomethacin can cause the syndrome of hyporeninemic hypoaldosteronism, probably by inhibiting prostaglandin biosynthesis.