title: Nonlinear accumulation of propranolol enantiomers.
abstract: The accumulation of (+)- and (-)-propranolol was investigated in nine subjects who received 160 mg of racemic propranolol as a single dose and then once daily for 7 days. The serum concentrations of propranolol enantiomers were measured by h.p.l.c. using a novel chiral stationary phase allowing direct resolution of underivatized propranolol. The (+)-propranolol AUC increased from 412 +/- 223 ng ml-1 h after single doses (0-infinity) to 584 +/- 279 ng ml-1 h at steady-state (0-24 h) (P less than 0.05). Similarly, (-)-propranolol AUC increased from 609 +/- 304 to 777 +/- 370 ng ml-1 h (P less than 0.05). The AUC ratio (-)/(+) was 1.52 +/- 0.36 and 1.32 +/- 0.17 after single doses and steady-state, respectively (P greater than 0.05). Therefore, nonlinear accumulation occurs with both enantiomers although there is a trend for the (-)/(+) ratio to decrease at steady-state.
authors.affiliation: Department of Clinical Pharmacy, University of Tennessee, Memphis 38163.
authors.forename: R L
authors.initials: RL
authors.lastname: Lalonde
authors.forename: M B
authors.initials: MB
authors.lastname: Bottorff
authors.forename: R J
authors.initials: RJ
authors.lastname: Straka
authors.forename: D M
authors.initials: DM
authors.lastname: Tenero
authors.forename: J A
authors.initials: JA
authors.lastname: Pieper
authors.forename: I W
authors.initials: IW
authors.lastname: Wainer
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D008297:Male; D011433:Propranolol / Q000493:pharmacokinetics*; D013237:Stereoisomerism
chemical_list: D011433:Propranolol