The effect of smoking on caffeine elimination was measured in 7 healthy volunteers and in 18 smoking and in 30 nonsmoking patients with alcoholic liver cirrhosis following oral application of 366 mg caffeine. In an intraindividual experiment in smoking health probands, caffeine clearance decreased from 118 +/- 33 to 77 +/- 22 ml per min (p less than 0.05) after abstaining cigarette smoking for 3 weeks. In a control group without liver disease (8 smokers, 15 nonsmokers), we found a caffeine clearance of 114 +/- 40 ml per min in smokers and 64 +/- 20 in nonsmokers (p less than 0.05). Smoking and nonsmoking patients with alcoholic liver cirrhosis did not differ with respect to clinical and laboratory data and hexobarbitone elimination. However, caffeine clearance was 63 +/- 63 ml per min in smoking patients compared to 34 +/- 49 ml per min in nonsmokers (p less than 0.05). Fasting plasma concentrations of caffeine were higher in nonsmokers (5.1 +/- 6.2 micrograms per ml) than in smokers (2.1 +/- 4.5 micrograms per ml, p less than 0.05). We conclude that smoking habits have to be taken into account if caffeine is used as a model compound for measuring quantitative liver function.

Adult↗

PubMedDate not supplied

Pharmacokinetic interactions with rifampicin.

Rifampicin, a potent antituberculosis agent, is frequently combined with other antituberculosis drugs, or with drugs belonging to entirely different classes which may be required during a long period of antituberculous treatment, and therefore has a potential for drug interactions of practical clinical importance. The absorption of rifampicin is markedly decreased when it is simultaneously administered with para-aminosalicylic acid granules, due to adsorption by an excipient, bentonite. Several clinical observations and investigations have indicated that rifampicin itself accelerates the metabolism of various other compounds, including oral anticoagulants, the contraceptive pill, oral hypoglycaemic agents and digitoxin. Rifampicin seems to be a potent inducer of drug metabolism in humans and it causes a proliferation of the smooth endoplasmatic reticulum and an increase of cytochrome P450 content in the liver. It also increases its own rate of desacetylation. However, of the test compounds hexobarbitone and tolbutamide, the metabolic clearance increased 2-to 3-fold following rafampicin treatment, whereas antipyrine clearance was unaltered. This indicates that there is a certain selectivity in the enzyme induction effect of rifampicin, although it reamins unclear which compound will and which will not be affected. Rifampicin may also possibly interfere with hepatic uptake of other compounds, but the clinical significance of this type of interaction has not been clearly demonstrated; On the other hand, oral probenecid significantly increases the serum level of rifampicin, probably due to a similar depression of hepatic uptake.

Absorption↗