There are no studies indicating a possible modification of imipenem pharmacokinetics related to the hour (i.e., circadian time) of its administration. The aim of this study was to evaluate the influence of different times of intramuscular imipenem administration on its disposition in Wistar AF EOPS rats. Four groups of eight animals were given a single intramuscular injection of 140 mg/kg of imipenem either at 10:00, 16:00, 22:00, or 04:00 h. Blood samples were collected 0.5, 1, 2, 3, 4, 6, and 8 h after drug injection, and the main pharmacokinetic parameters determined were C(max), T(max), elimination half-life (t(1/2)), area under the concentration-versus-time curve (AUC), total serum clearance (CL/F), and volume of distribution (V/F). Circadian variation of C(max) (49%), T(max) (92%), and AUC (19%) was observed leading to variability of imipenem exposure. Clearance and volume of distribution were modified according to the circadian time of drug injection but did not reach statistical significance. The results suggest that varying the time of administration induces intra-individual variability.

The pharmacokinetics of indomethacin (Indo) was studied in 10 healthy elderly male volunteers (age 67–81 years) following the oral administration of a single 75-mg dose of a sustained release form of Indo. The total and free plasma and erythrocyte concentrations of Indo were determined by a specific high-pressure liquid chromatographic method. A maximum concentration (C_max) of 4.28 ± (SE) 0.43 μg/ml was reached after 1.85 ± 0.22 h. The area under the plasma concentration versus time curve (AUC) was 22.83 ± 2.70 μg ml-¹ h and the plasma elimination half-life was 4.34 ± 0.64 h. The maximum concentration of Indo in the red blood cells was 0.123 ± 0.013 μg/ml and was obtained at 1.95 ± 0.14 h after drug administration. The erythrocyte concentrations of Indo represented 2.4% of the total plasma levels of Indo whereas only 1.3% of the drug was unbound to plasma proteins. The C_max and AUC values determined in the elderly were approximately double the values reported in young adults for the same dose.

Seven asthmatic patients were given a single placebo tablet in a first test session and then in two subsequent double blind sessions they randomly received 400 mg bevantolol or 100 mg atenolol, with at least 2 days between each of the sessions. Neither beta-blocker had any significant effect on FVC as compared to the placebo. FEV 1, however, was significantly lower 2 and 3 h after atenolol or bevantolol; there was no significant difference between the effects of the two drugs on FEV 1. Peak expiratory flow rate was reduced by bevantolol but not by atenolol, the difference reaching significance after 3 h. Fenoterol inhalation at the end of each test session always enhanced pulmonary performance, but to a lesser extent after bevantolol than after placebo or atenolol. A slower heart rate was recorded 2, 3, and 4 h after bevantolol and 3 and 4 h after atenolol; the mean 2-h value was significantly lower with atenolol than with bevantolol. No patient suffered any adverse effect. Bevantolol may be slightly less selective than atenolol.

No abstract

The purpose of this study was to determine the relationship between inflammation, increased alpha-1-acid glycoprotein (AAG), and lidocaine tolerance during fiber-optic bronchoscopy. Previous studies indicate that serum lidocaine levels vary widely from one individual to another. One reason for these variations may be the presence of an ongoing inflammatory process, which enhances serum AAG, a major binding protein of lidocaine. To test this hypothesis, we assayed free and bound lidocaine as well as AAG in the blood of 12 patients after administration of 9 mg/kg of lidocaine during fiber-optic bronchoscopy. Some of the subjects had clear evidence of inflammation or infection. A correlation was found between AAG and total and bound lidocaine but not between AAG and free lidocaine (which remained almost constant). Thus, in spite of the high total levels of lidocaine observed in some patients with inflammatory processes, the free fraction (which is the active and toxic fraction) remained low.