Drugs online research references
J Pharmacol Exp Ther. 1981 Jun;217(3):602-10.
Radioimmunoassay and pharmacokinetic profile of bupropion in the dog.
Butz RF, Schroeder DH, Welch RM, Mehta NB, Phillips AP, Findlay JW.
A radioimmunoassay (RIA) procedure for the quantification of bupropion (dl-2-tert-butylamino-3'-chloropropiophenone) in biological fluids is described. Immunization of rabbits with conjugates of bovine serum albumin and p-succinoyl propylbupropion or p-carbomethoxybupropion resulted in the production of antisera which are capable of detecting less than 1 ng ml-1 (100 pg actual mass) of bupropion in the RIA, utilizing [6-3H] bupropion as radioligand. The antisera used in these studies have low cross-reaction (approximately 0.1% or less) with known side chain metabolites of bupropion, but exhibit significant cross-reaction with p-hydroxybupropion (30.3%). Excellent agreement was obtained between RIA and high-pressure liquid chromatography determinations of bupropion concentrations in human plasma samples, but plasma or serum from bupropion-treated dogs, rats and mice required extraction from basic medium to remove some interference before RIA. The assay was applied to a study of bupropion disposition in two beagles of each sex after i.v. and p.o. administrations of bupropion hydrochloride (100 mg). The pharmacokinetic profile in dogs was best described by an open two-compartment model after either route of drug administration. Peak plasma bupropion levels after oral dosing were highly variable, ranging from 12.9 to 63.5 ng ml-1 at 26 to 32 min after drug administration. The mean terminal phase half-life of bupropion was calculated to be 1.73 hr after either route and the absolute oral bioavailability of the drug varied from 2.0 to 6.5%.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6785419&dopt=Abstract
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Pharmacol Biochem Behav. 1981 Nov;15(5):743-6.
Drug alterations of punished responding after chlordiazepoxide: possible screen for agents useful in minimal brain dysfunction.
Pappas BA, Vogel RA, Wilson JH, Mueller RA, Breese GR.
In the present study, the effect of various stimulant drugs on the action of chlordiazepoxide to increase punished responding was studied. Drugs such as d-amphetamine, methylphenidate and imipramine that are effective in attentional deficit disorder (MBD) were found to reverse this benzodiazepine-induced increase in responding. Phenobarbital which worsens this condition enhanced the benzodiazepine effect. Since the impairment caused by chlordiazepoxide may be analogous to the lack of impulse control noted in MBD, the bupropion antagonism of this action of chlordiazepoxide suggests that bupropion may be useful in MBD.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6796972&dopt=Abstract
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Eur J Clin Pharmacol. 1981;21(2):127-35.
Pharmacokinetics of bupropion, a novel antidepressant agent, following oral administration to healthy subjects.
Findlay JW, Van Wyck Fleet J, Smith PG, Butz RF, Hinton ML, Blum MR, Schroeder DH.
The pharmacokinetics of bupropion hydrochloride, a structurally novel antidepressant agent, have been studied in healthy male and female subjects following administration of single oral doses of 50, 100 and 200 mg. Plasma drug concentrations were determined directly by a specific radioimmunoassay (r.i.a.), while urinary measurements required a prior solvent extraction to remove substances interfering in the assay. Bupropion appeared rapidly in the plasma, suggesting good absorption. Drug plasma concentration-time data were fitted well to a two-compartment open model of drug disposition by use of the computer program NONLIN. By comparison of AUC, Cmax and tmax values, the pharmacokinetics of bupropion were found to be linear across the 50-200 mg dose range in both sexes. When the data were normalized for subjects' body weights, no differences between pharmacokinetic parameters for male and female subjects were found. Mean disposition half-lives across treatments were 1.2-1.4 h for t1/2 alpha and 10.7-13.8 h for the t1/2 beta. Bupropion was extensively bound (85%) to human plasma proteins over a wide drug concentration range. Less than 1% of a 200 mg oral dose of bupropion hydrochloride appeared in the urine of 16 subjects as unchanged drug, indicating extensive metabolism of the parent compound.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6804243&dopt=Abstract
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