IN VITRO AND IN VIVO EVALUATION OF THE CLEARANCE OF ACETAMINOPHEN AND PHENOBARBITAL BY A SORBENT SUSPENSION RECIPROCATING DIALYZER
Abstract
Acetaminophen and phenobarbital are medicinal agents which may be involved in overdose situations. The use of the sorbent suspension reciprocating dialyzer (SSRD) in the treatment of the excessive intake of these drugs was studied. The SSRD is a parallel plate dialyzer with a reciprocating blood flow and freely mobile sorbent suspension composed of powdered charcoal and zeolites. This provides a system with minimal sorbent saturation. The clearances of acetaminophen and phenobarbital by the dialyzer were studied in vitro and in vivo in normal dogs. High pressure liquid chromatography assays were developed for the quantification of the drugs in aqueous and serum fluids. Acetaminophen and phenobarbital were extracted from the samples by a one-step extraction procedure using ethyl acetate. The methods had a sensitivity of 1 ug/ml. Activated charcoal has a higher adsorption capacity for acetaminophen (194.2 mg/g) compared to phenobarbital (102 mg/g). The presence of methyl cellulose in the charcoal suspension did not affect the adsorption capacity of charcoal particles. The mass transfer coefficient at the 50 percent removal efficiency obtained during in vitro fractional tests, was 9.95 x 10('-3) cm/min for acetaminophen and 6.7 x 10('-3) cm/min for phenobarbital. The rate of removal of acetaminophen and phenobarbital remained relatively constant throughout 10 hours of continuous in vitro dialysis. Following intravenous administration of large doses of acetaminophen and phenobarbital, the elimination half-lives were 1.84 and 72.7 hours for the drugs, respectively. During in vivo dialysis studies, the elimination half-life of acetaminophen before dialysis was significantly different from the value during dialysis. The half-lives were not significantly different during and after dialysis. The half-life of phenobarbital during dialysis was significantly shorter than the values after dialysis. The mean dialyzer clearances for acetaminophen and phenobarbital were 59.0 and 49.0 ml/min, respectively. A significant amount of phenobarbital was removed during four hours of dialysis (44%) while a smaller amount of acetaminophen was removed (18%) in the same time. The SSRD is an efficient device for the treatment of phenobarbital overdose, but less likely beneficial in acetaminophen overdose, unless operated for long times (8 to 10 hours).
Degree
Ph.D.
Subject Area
Pharmacology
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