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Dive into the research topics where Steven S. Good is active.

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Featured researches published by Steven S. Good.


Clinical Pharmacology & Therapeutics | 1989

Alteration of zidovudine pharmacokinetics by probenecid in patients with AIDS or AIDS‐related complex

Paulo de Miranda; Steven S. Good; Robert Yarchoan; Rose V Thomas; M. Robert Blum; Charles E Myers; Samuel E. Broder

The anti–human immunodeficiency virus drug zidovudine is metabolized extensively in human beings to the 5′‐glucuronide (GAZT) and is cleared rapidly, resulting in a short half‐life and the need for frequent dosing. This study explores whether probenecid, which is also metabolized by glucuronidation, reduces zidovudine clearance when zidovudine is adminstered orally to patients with acquired immunodeficiency syndrome (AIDS) or AIDS‐related complex (ARC). The mean zidovudine plasma levels were significantly higher after concurrent administration of probenecid than in its absence, resulting in a twofold increase in the mean AUC, a corresponding decline in the apparent total clearance, and a prolongation in the mean half‐life. Similar alterations were observed in GAZT disposition. There was a marked reduction in the urinary excretion ratio of GAZT to zidovudine and a decline in the renal clearance of GAZT after probenecid coadministration. Probenecid inhibits zidovudine glucuronidation and renal excretion of GAZT.


Analytical Biochemistry | 1979

A sensitive radioimmunoassay for the antiviral agent BW248U [9-(2-hydroxyethoxymethyl)guanine]☆

R.P. Quinn; P. de Miranda; Leroy Gerald; Steven S. Good

Abstract A sensitive radioimmunoassay (RIA) for the new antiviral agent, BW248U [9-(2-hydroxyethoxymethyl)guanine], has been developed. The antisera used in the assay were obtained by immunizing rabbits with a succinyl-BW248U-rabbit serum albumin conjugate. In the assay, a single tube per sample is employed throughout, succinyl-[3H]BW248U is used as the antigen, and only 0.1 ml of sample per tube is required. The procedure does not require sample extraction, and ammonium sulfate is used as the precipitating agent. The RIA has a useful range of 0.05 to 50 nmol of BW248U/ml and the concentrations of the drug determined by this method are in good agreement with those obtained by high-performance liquid chromatography. Naturally occurring purine bases and nucleosides, as well as a wide variety of nonrelated drugs, do not interfere with the assay. When antiserum from one rabbit was employed, the association constant with succinyl-[3H]BW248U was found to be 2.05 × 108 liters/mol while that for [3H]BW248U was 10-fold less.


Antiviral Chemistry & Chemotherapy | 1992

Species Differences in the Metabolism and Disposition of Antiviral Nucleoside Analogues: 1. Acyclovir

P. de Miranda; Steven S. Good

The acyclic nucleoside analogue, acyclovir, is an antiviral drug with activity against the herpes group of DNA viruses. Clinically, it is used as a selective therapeutic agent for the treatment of herpes simplex and varicella-zoster virus infections. Studies on the disposition of acyclovir, during the course of its preclinical and clinical development, indicated significant species differences in the absorption, metabolism and elimination of the drug. Gastrointestinal absorption was adequate in dogs and in mice; but in rats and primates it was limited to less than 20% of the administered dose. Whereas in some species (mice, rats, and dogs), acyclovir was virtually unmetabolized, significant biotransformation was apparent in guinea pigs, rabbits, and some primates. Acyclovir tissue distribution was extensive and indicated few differences across species. This review summarizes diverse studies on acyclovir absorption, metabolism, and disposition in different species, including humans, and indicates the relevance and importance of such studies in drug development.


The American Journal of Medicine | 1982

Metabolic fate of radioactive acyclovir in humans

Paulo de Miranda; Steven S. Good; Harvey C. Krasny; James D. Connor; Oscar L. Laskin; Paul S. Lietman

The metabolic fate and the kinetics of elimination of [8-14C]acyclovir in plasma and blood was investigated in five cancer patients. Doses of 0.5 and 2.5 mg/kg were administered by one-hour intravenous infusion. Radioactivity was distributed nearly equally in blood and plasma. The plasma and blood concentration-time data were defined by a two-compartment open pharmacokinetic model. The overall mean acyclovir plasma half-life and total body clearance +/- SD were 2.1 +/- 0.5 hours and 297 +/- 53 ml/min/1.73 m2. Binding of acyclovir to plasma proteins was 15.4 +/- 4.4 percent. The radioactive dose was excreted predominantly in the urine (71 to 99 percent) with less than 2 percent excretion in the feces and only trace amounts of radioactivity in the expired air. Reverse-phase high-performance liquid chromatography indicated that 9-carboxymethoxymethylguanine was the only significant urinary metabolite of acyclovir accounting for 8.5 to 14.1 percent of the dose. A minor metabolite (less than 0.2 percent of dose) had the retention time of 8-hydroxy-9-(2-hydroxyethoxymethyl)guanine. Unchanged urinary acyclovir ranged from 62 to 91 percent of the dose. There was no indication of acyclovir cleavage to guanine. The renal clearances of acyclovir were three times higher than the corresponding creatinine clearances.


The American Journal of Medicine | 1982

Metabolic disposition of acyclovir in the guinea pig, rabbit, and monkey

Steven S. Good; Paulo de Miranda

Two guinea pigs and two rabbits were each inoculated subcutaneously with 14C-labeled acyclovir (25 mg/kg). Both species excreted the entire amount within 72 hours. The rabbits excreted all of the radioactivity in the urine while the guinea pigs excreted an average of 14.2 percent in the feces. The rabbits excreted an average of 71.0 percent of the dose as unchanged drug; 25.1 percent was excreted as 9-carboxymethoxymethylguanine (CMMG) and 3.5 percent as 8-hydroxy-9-(2-hydroxyethoxymethyl)guanine (8-hydroxyacyclovir). An average of 60.7 percent of the dose was recovered from the guinea pigs as acyclovir; 32.3 percent was excreted as CMMG and 3.1 percent as 8-hydroxyacyclovir. The two rabbits showed elimination-phase half-lives (t 1/2 beta) for plasma acyclovir of 0.8 and 2.2 hours. Mean t 1/2 beta for acyclovir in two rhesus, four patas, and four african green monkeys, each receiving acyclovir (10 mg/kg) as a bolus intravenous injection, were 1.2, 1.7, and 1.8 hours respectively. The average 48 hour urinary excretion of acyclovir, 8-hydroxyacyclovir, and CMMG in the rhesus monkey was estimated to be 21.3 percent, 15.3 percent, and 7.1 percent, respectively, of the total administered amount. The patas and african green species excreted the dose mostly as acyclovir and CMMG.


Analytical Biochemistry | 1983

A single-tube radioimmunoassay for the antiviral agent 2,6-diamino-9-(2-hydroxyethoxymethyl)purine (A134U)

R.P. Quinn; Steven S. Good; Leroy Gerald; Julie J. Sabatka

A direct radioimmunoassay for the detection of A134U in biological fluids and extracts has been developed. The entire assay, including scintillation counting, is performed using 12 X 55-mm centrifuge tubes and results in a sensitive, reliable, and relatively inexpensive procedure. The log-logit transformation is linear over a range of 1 to 30 pmol per sample. Intra-assay precision was found to be excellent with a coefficient of variation ranging from 4.1 to 14.5% for the standard curve with plasma and a coefficient of variation ranging from 4.0 to 17.8% for the standard curve with urine. Interassay precision and accuracy were also found to be good. With the antisera chosen for use, no cross-reactivity was found with acyclovir or its two known metabolites, while some cross-reactivity was seen with the corresponding two derivatives of A134U. Only very minor cross-reactivities were seen with a small number of other compounds out of a large number tested.


Journal of Chromatography B: Biomedical Sciences and Applications | 1988

Simultaneous quantification of zidovudine and its glucuronide in serum by high-performance liquid chromatography

Steven S. Good; David J. Reynolds; Paulo de Miranda


Drug Metabolism and Disposition | 1990

Isolation and characterization of an ether glucuronide of zidovudine, a major metabolite in monkeys and humans.

Steven S. Good; C S Koble; R Crouch; R L Johnson; J.L. Rideout; P de Miranda


Drug Metabolism and Disposition | 1990

Tissue distribution and metabolic disposition of zidovudine in rats.

P de Miranda; Thimysta C. Burnette; Steven S. Good


Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) | 1986

Biotransformation in various species and in humans of 3'-azido-3'-deoxythymidine, a potential agent for the treatment of AIDS

Steven S. Good; D.T. Durack; P. de Miranda

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R.P. Quinn

Research Triangle Park

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Gertrude Belle Elion

University of Alabama at Birmingham

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