Antibiotics and oral contraceptives

With the exception of rifampin-like drugs, there is a lack of scientific evidence supporting the ability of commonly prescribed antibiotics, including all those routinely employed in outpatient dentistry, to either reduce blood levels and/or the effectiveness of oral contraceptives. To date, all clinical trials studying the effects of concomitant antibiotic therapy (with the exception of rifampin and rifabutin) have failed to demonstrate an interaction. Like all drugs, oral contraceptives are not 100 per cent effective with the failure rate in the typical United States population reported to be as high as 3 per cent. It is thus possible that the case reports of unintended pregnancies during antibiotic therapy may simply represent the normal failure rate of these drugs. Considering that both drug classes are prescribed frequently to women of childbearing potential, one would expect a much higher rate of oral contraceptive failure in this group of patients if a true drug:drug interaction existed. On the other hand, if the interaction does exist but is a relatively rare event, occurring in, say, 1 in 5000 women, clinical studies such as those described in this article would not detect the interaction. The pharmacokinetic studies of simultaneous antibiotic and oral contraceptive ingestion, and the retrospective studies of pregnancy rates among oral contraceptive users exposed to antibiotics, all suffer from one potential common weakness, i.e., their relatively small sample size. Sample sizes in the pharmacokinetic trials ranged from 7 to 24 participants, whereas the largest retrospective study of pregnancy rates still evaluated less than 800 total contraceptive users. Still, the incidence of such a rare interaction would not differ from the accepted normal failure rate of oral contraceptive therapy. The medico-legal ramifications of what looks like at best a rare interaction remains somewhat "murky." On one hand, we have medico-legal experts advising the profession to exercise caution and warn all oral contraceptive users of a potential reduction in efficacy during antibiotic therapy. These opinions are not evidence-based and rely heavily on one or two legal proceedings that cannot even be substantiated. On the other hand, there is one recently published legal proceeding in which the outcome was in favor of the oral surgeon. There is clearly...

Effect of activated charcoal on rifampicin absorption in man.

The effect of activated charcoal (AC) on rifampicin excretion was investigated in six healthy volunteers. On three occasions, at weekly intervals, each subject received a 600 mg rifampicin with 350 ml of water; b+c one and two weeks later, 600 mg of rifampicin plus 7.5 and 15 g AC, respectively, in 350 ml of water as a charcoal slurry. Urinary levels of rifampicin were measured form 1-36 hr after ingestion. Treatment with AC led to 1.2 per cent urinary recovery of rifampicin; decreased excretion rate; and a much lower plateau indicative of reduced absorption.

Pharmacokinetics of clofazimine in healthy volunteers.

The pharmacokinetics of clofazimine was evaluated in 12 healthy male volunteers following single and multiple oral doses of clofazimine. Six volunteers received a single dose of 200 mg together with food. A 200-mg dose was administered to three volunteers either with or without food. In a multiple-dose experiment, three volunteers were repeatedly dosed with 50 mg per day together with food for 8 days. Following a single oral dose of 200 mg, the mean peak plasma concentration of clofazimine was 861 +/- 289 pmol/g (+/- S.D., N = 6) after 8 hr (median). The mean terminal half-life was 10.6 +/- 4.0 days. Comparison of the bioavailability of clofazimine administered with or without food revealed a 60% higher mean area under the curve (AUC) value and a 30% higher mean maximum concentration (Cmax) value with food (N = 3). The median of times to peak (Tmax) was 8 hr with food and 12 hr without food. In the multiple-dose study, good agreement was found between the mean experimental plasma concentration values and the plasma concentration profile predicted from the single-dose pharmacokinetics. The elimination half-life calculated from the terminal phase of the individual profiles after the last dose was 8.8 +/- 1.0 days (+/- S.D., N = 3). The half-life obtained from the fitted mean multiple-dose profile was 10.5 days. The slow elimination of clofazimine has its implications for the treatment regimen in patients. To avoid the long-lasting accumulation toward the steady state, higher daily loading doses are recommended at the beginning of therapy followed by a daily maintenance dose.

Effect of clofazimine: detailed studies of small intestine functions.

Twenty one patients of leprosy were studied for gastrointestinal symptoms and submitted to detailed intestinal absorption tests and jejunal biopsy before and after the institution of Clofazimine therapy. Fifteen patients were administered 100 mg orally daily for 3 months, while six patients with ENL received 300 mg of the drug for 6 weeks initially and then 100 mg daily. Mild diarrhoea and abdominal symptoms occurred in four patients, fecal fat excretion increased in one patient but Schilling's and d-Xylose tests did not alter. No significant changes were produced by Clofazimine therapy in jejunal mucosa. Clofazimine crystals were seen in the lamina properia of one patient, the overlying mucosa was normal. No correlation was found between the abnormality in mucosal pattern, crystal deposition, absorption parameters or symptomatology and doses of drug taken.

Evaluation of effectiveness of clofazimine therapy. I. Monitoring of absorption of clofazimine from gastrointestinal tract.

The quantity of clofazimine absorbed from the gastrointestinal tract when administered to lepromatous leprosy patients at varying single doses of 600 mg., 400 mg., 300 mg., and 100 mg. has been worked out by determining the amount of clofazimine present in total faecal excreta. Except in 100 mg. dose where the percentage absorption was 62.5 +/- 17 in all other case the values were around 45%. The efficacy of daily administration of 100 mg. clofazimine is discussed in this first article.

Structure and function of the small bowel in lepromatous leprosy.

The structural and functional status of the small bowel was examined in ten patients with lepromatous leprosy. The absorptive functions were essentially normal in all patients except for minor abnormalities; one patient had mild steatorrhea and two others had derangement of D-xylose absorption. Barium examination did not reveal any abnormality in any patient. Histological study of the small intestinal mucosa showed mild, partial villous atrophy in two patients and normal appearances in the remaining eight. The above abnormalities were mild and were not considered to be of any clinical significance. It is therefore concluded that the small bowel is not commonly involved in lepromatous leprosy.

Xylose absorption in Papua New Guineans with leprosy.

Blood xylose concentrations were measured at 60, 90 and 120 min after 25 xylose was given orally in 33 well-nourished Papua New Guinean in-patients at Port Moresby; 12 had lepromatous (group A) and seven non-lepromatous (group B) leprosy, and 14 were controls (group C). Differences between mean xylose concentrations were not significant at any time interval. Three patients (two in group A and one in group B) had 90 min xylose concentrations less than 2.0 mmol l-1. There was no association between xylose concentration and current therapy. Leprosy does not impair small-intestinal absorptive function; it therefore differs from other chronic infections, in which there is xylose malabsorption.

Estudio de biodisponibilidad en dos preparaciones distintas de rifampicina / Bioavailability of 2 different rifampicin preparations

Blood levels of two different preparations of Rifampicin were determined after a standard dose of 600mg. Three hours later, blood concentrations showed no statistical differences. Six hours later the levels were statiscally significant well above the minimum inhibitory levels for Mycobacterium Tuberculosis. For practical purposes it may be said that no diference in th bioavailability existis between the two drugs studied...