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Nonlinear accumulation of propranolol enantiomers.
Author(s) -
Lalonde RL,
Bottorff MB,
Straka RJ,
Tenero DM,
Pieper JA,
Wainer IW
Publication year - 1988
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1988.tb03371.x
Subject(s) - propranolol , enantiomer , chemistry , steady state (chemistry) , chromatography , pharmacology , endocrinology , medicine , stereochemistry
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.