Nonlinear accumulation of propranolol enantiomers.

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. 1988 The British Pharmacological Society