Vancomycin pharmacokinetics in acute renal failure: preservation of nonrenal clearance.

INTRODUCTION: The normal nonrenal clearance of vancomycin is reduced in patients with chronic renal failure (40 versus 6 ml/min). The nonrenal clearance of vancomycin in patients with acute renal failure has not been characterized extensively. PURPOSE: To prospectively determine the pharmacokinetic profile of vancomycin in anuric patients with acute renal failure who are receiving continuous venovenous hemofiltration. METHODS: Vancomycin serum samples were obtained in 10 patients immediately before and 1 and 12 hours after a 1-hour infusion. Thirteen sets of data were obtained. Vancomycin concentration data were incorporated into a first-order, single-compartment model. Determinations for the area under the serum concentration-time curve were made by the trapezoidal rule. RESULTS: Total vancomycin clearance was 28.5 +/- 6.4 ml/min (range, 17.1 to 36.6 ml/min. Hemofilter clearance was either 6.7 or 13.3 ml/min, depending on ultrafiltrate production rate (assuming a sieving coefficient of 0.8). Nonrenal clearance, calculated as total clearance minus hemofilter clearance was 16.2 +/- 7.0 ml/min (range, 3.8 to 23.3 ml/min). Total clearance did not correlate with hemofilter clearance (r = 0.1; p greater than 0.25) but correlated strongly with nonrenal clearance (r = 0.94; p less than 0.0005). Nonrenal clearance decreased significantly as the days on continuous venovenous hemofiltration increased (range, 2 to 14 days; r = 0.68; p less than 0.025). CONCLUSION: Early in the course of acute renal failure there is a substantial preservation of the normal nonrenal clearance of vancomycin. This nonrenal clearance appears to decrease with the duration of renal failure, eventually approaching the clearance observed in patients with chronic failure.

Terfenadine pharmacokinetics in breast milk in lactating women.

The excretion of terfenadine into breast milk has not been reported previously. Disposition of terfenadine was prospectively studied in four healthy lactating mothers (age, 33 +/- 4 years). Subjects received 60 mg terfenadine every 12 hours over a period of 48 hours to achieve steady-state milk and plasma concentrations. Milk and plasma samples were collected at 1/2, 1, 1 1/2, 2, 3, 4, 6, 8, 12, 24, and 30 hours after the last dose. Terfenadine and its active metabolite milk and plasma concentrations were quantitated by HPLC. Terfenadine was not detected in milk or plasma. Mean +/- SD active metabolite data for milk and plasma are as follows: Cmax (ng/ml), 41.0 +/- 16.4 for milk, 309.0 +/- 120.5 for plasma; tmax (hours), 4.3 +/- 2.4 for milk, 3.9 +/- 3.0 for plasma; t1/2 beta (hours), 14.2 +/- 5.4 for milk, 11.7 +/- 6.4 for plasma; AUC(0-12) (ng.hr/ml) 320.4 +/- 99.8 for milk, 1590.0 +/- 300.4 for plasma. Metabolite milk/plasmaAUC(0-12) ratios ranged from 0.12 to 0.28 (mean, 0.21 +/- 0.07). Newborn dosage estimates based on the highest measured concentration of terfenadine metabolite in milk suggests the maximum level of newborn exposure would not exceed 0.45% of the recommended maternal weight-corrected dose. Estimated amounts consumed by the neonate after the mother is given the recommended dose of the drug are not likely to result in plasma levels producing untoward effects.

G-CSF and GM-CSF.

Filgrastim and sargramostim are hematopoietic growth factors that are now produced on a large scale through recombinant DNA technology. Both agents are effective in increasing blood cell counts following chemotherapy and bone marrow transplantations. Investigational work is still being conducted to determine their potential use.

Comparison of imipenem pharmacokinetics in patients with acute or chronic renal failure treated with continuous hemofiltration.

The total clearance of imipenem, a carbapenem antibiotic, is reduced from approximately 230 mL/min in patients with normal renal function to approximately 50 mL/min in patients with chronic renal failure. This decline in clearance results not only from the loss of renal clearance, but also from a reduction in the nonrenal clearance from 130 to 50 mL/min. Current dosing recommendations for the administration of imipenem to patients with acute or chronic renal failure are based on this reduced clearance rate. We investigated the pharmacokinetics of imipenem in critically ill patients with acute or chronic renal failure to determine whether published dosing guidelines were applicable to both patient populations. Imipenem pharmacokinetic parameters were determined in 10 anuric patients with renal failure managed by continuous venovenous hemofiltration (CVVH). Seven patients had acute renal failure, while the other three had preexisting chronic renal failure. Imipenem serum concentration data were incorporated into a first-order, single-compartment pharmacokinetic model. Determinations of the area under the serum concentration-time curve were made by the trapezoidal rule. Dosing regimens were calculated from clearance data to achieve a mid-dose imipenem serum concentration of 12 mg/L. The total clearance of imipenem in patients with acute renal failure (108.3 +/- 13.8 mL/min; mean +/- SD) was significantly greater than the total clearance measured in patients with chronic renal failure (64.4 +/- 10.5 mL/min; P < 0.02). This increased clearance resulted from a greater nonrenal clearance of the drug in patients with acute renal failure (95.0 +/- 13.8 v 51.1 +/- 10.5 mL/min; P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous venovenous hemofiltration: an alternative to continuous arteriovenous hemofiltration and hemodiafiltration in acute renal failure.

Continuous venovenous hemofiltration (CVVH) has been used as an alternative to continuous arteriovenous hemofiltration (CAVH) and hemodiafiltration (CAVHD) in the management of critically ill patients with acute renal failure. This report describes our experience with the first 25 patients treated with CVVH at our institution. Vascular access was obtained through a single dual-lumen venous catheter. A blood pump was used to provide ultrafiltration pressure. An ultrafiltrate pump was incorporated to ensure predictable ultrafiltrate production rates. Safety features in the extracorporeal circuit included a venous drip chamber with bubble detector and an in-line pressure monitor. CVVH was initiated by a nephrologist and dialysis nurse and was maintained by the intensive care unit (ICU) nursing staff. Fifteen females and 10 males received CVVH therapy for a total of 193.5 days (average, 7.7 +/- 10.3 days; range, 0.5 to 48 days). Four of the 25 patients (16%) survived and were discharged from the hospital. Four additional patients (16%) survived the acute phase of their illness, but died from complications of their primary disease before discharge from the hospital. The mean weight change during CVVH was -7.9 +/- 7.0 kg (range, -26.5 to +2.9 kg). Metabolic waste products and electrolytes were adequately controlled by CVVH in all but one hypercatabolic patient. The mean heparin dose required was 6.5 +/- 4.2 U/kg/h and was adjusted to prevent filter clotting rather than to achieve a predetermined activated partial thromboplastin time (PTT). The median PTT was 35.8 seconds (range, 22.0 to 100; control, 19.5 to 29.5 seconds). Four episodes of volume-responsive hypotension occurred during the 193.5 treatment days. Only one patient experienced a hemorrhagic complication during CVVH. No patient experienced a complication related to vascular access. Twelve of 111 total hemofilters were changed because of clot formation. CVVH was well tolerated by patients and managed efficiently by the ICU nursing staff.(ABSTRACT TRUNCATED AT 250 WORDS)