Pharmacokinetic studies of rifampicin in the elderly.

The pharmacokinetics of rifampicin (RMP) and its principal active metabolite desacetylrifampicin (DA-RMP) were studied in six subjects, ranging in age from 78 to 95 years, after single oral doses of 10 mg/kg RMP. The maximal plasma concentrations (Cmax) and the elimination half-lives (t 1/2 beta) of RMP are 8.83 +/- 1.72 mg L-1 and 4.09 +/- 2.59 h, respectively. They are comparable to those reported in young adults. The same applies to the Cmax value (1.93 +/- 0.53 mg L-1) and t 1/2 beta value (4.65 +/- 2.61 h) of DA-RMP. However, the renal clearance of RMP (0.0075 +/- 0.0036 L h-1) and the amounts of RMP (20.7 +/- 9.9 mg) and DA-RMP (13.3 +/- 5.6 mg) excreted in the urine during a 24-h period are lower than those reported in young adults. The renal excretion of RMP and DA-RMP, therefore, is reduced in the elderly. But since the drug is also excreted through the liver to such an extent that serum levels are the same as in young adults, for therapeutic purposes the metabolism of RMP may be globally considered as unaltered in elderly patients.

Contribution of prostaglandins and thromboxanes to the adenosine and ATP-induced contraction of guinea-pig isolated trachea.

1 In in vitro experiments adenosine 5'-triphosphate (ATP) and adenosine were found to exert different effects on the guinea-pig isolated trachea depending on whether the trachea had previously been contracted with acetylcholine (ACh) (6.6 x 10(-6) M) or was at resting tone. 2 ATP and adenosine (10(-5) and 10(-3) M) were equipotent in relaxing the precontracted guinea-pig trachea, since concentrations of 1.09 +/- 0.35 and 0.39 +/- 0.16 mM respectively reduced by 25% the ACh-induced contraction. 3 ATP and adenosine (10(-5) and 10(-4) M) caused a moderate contraction of the guinea-pi trachea under resting tone. This effect was antagonized by inhibitors of cyclo-oxygenase (indomethacin 10(-6) M, aspirin 0.3 x 10(-3) M and 3 x 10(-3) M) and of thromboxane synthetase (nictindole 10(-7) M, imidazole 5 x 10(-5) M), which suggests an indirect mechanism of action with release of arachidonic acid derivatives.