Pharmacokinetics of tenidap sodium administered with food or antacid in healthy volunteers.

1. The effects of food and antacid on the pharmacokinetics of tenidap were investigated in this randomised, 3-way cross-over study. 2. Twenty-one healthy young men, mean age 27.4 years, received single oral doses of tenidap sodium 120 mg at weekly intervals after either an overnight fast, with food or with 20 ml of the antacid Maalox (aluminum hydroxide 1.8 g and magnesium hydroxide 1.2 g). Plasma samples collected immediately before and up to 96 h after each tenidap dose were assayed for tenidap using a validated h.p.l.c. method. The assay data were used to determine the pharmacokinetic parameters of tenidap in each group. 3. Co-administration of tenidap with food produced a statistically significant delay in the rate of absorption (tmax, 4.4 h) (P < 0.001). There was no statistically significant change in Cmax. However, co-administration with the antacid significantly decreased both the mean rate and extent of absorption of tenidap compared with the fasting state: AUC, 420.93 micrograms ml-1 h (antacid), 476.31 micrograms ml-1 h (fasting) (P = 0.026); Cmax 14.3 micrograms ml-1 (antacid), 18.0 micrograms ml-1 (fasting) (P = 0.001); tmax 4.5 h (antacid), 2.9 h (fasting) (P < 0.001). Neither food nor the antacid had any effect on the elimination of tenidap. These changes in tmax are unlikely to be of any clinical significance owing to the long half-life of tenidap. 4. Treatment was well tolerated. Only two adverse events were reported that were considered by the investigator to be related to tenidap. There were no reports of laboratory or cardiovascular abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

An investigation into the effect of tenidap sodium on the pharmacokinetics of a combined oral contraceptive.

1. The effects of tenidap sodium and placebo on the pharmacokinetics of a combined oral contraceptive (Microgynon 30) were evaluated in 18 healthy premenopausal women in a double-blind, cross-over study lasting two menstrual cycles. 2. Tenidap (120 mg day-1) or placebo was given for 11 days, starting within 4 days of menstruation and Microgynon 30, containing levonorgestrel (150 micrograms) and ethinyloestradiol (30 micrograms), was administered on day 10 of tenidap therapy. 3. The mean maximum plasma levonorgestrel concentrations (Cmax), time to Cmax (tmax) and area under the plasma time-concentration curves (AUC(0,t)) did not differ between subjects given tenidap or placebo. The Cmax, tmax and AUC(0,t) values for ethinyloestradiol did not differ between tenidap and placebo recipients. Only the ethinyloestradiol Cmax showed a significant difference (P = 0.02) between menstrual cycles 1 and 2 (252.9 pg ml-1 and 271.3 pg ml-1, respectively). 4. Co-administration of tenidap and Microgynon 30 was well tolerated and no subject withdrew from the study because of side-effects. There were no side-effects considered to be related to tenidap and no clinically significant laboratory abnormalities were considered to be related to treatment. 5. The results of the study suggest that the pharmacokinetics of the oestrogen and progestin components of the oral contraceptive Microgynon 30 are unlikely to be affected by concomitant administration of tenidap.

PIP: In Belgium, clinicians enrolled 18 healthy premenopausal women attending the St. Remi Clinic in Brussels in a double-blind, cross-over study lasting two menstrual cycles to examine the effect of the new anti-rheumatic drug, tenidap sodium, on the pharmacokinetics of a combined oral contraceptive (OC) containing 150 mcg levonorgestrel and 30 mcg ethinyl estradiol. Beginning with the fourth day of menstruation, the women received either an oral dose of three 40 mg capsules or a matched placebo once a day over 11 days during the first menstrual cycle. During the second cycle, they received the treatment that they did not receive during the first cycle. Regardless of cycle, they received the OC (Microgynon 30) on day 10 of tenidap therapy. There was no appreciable difference in mean maximum plasma levonorgestrel concentrations (Cmax), time to Cmax (tmax), and area under the plasma time-concentration curves (AUC[0,t]) between the tenidap group and the placebo group. The same was true for ethinyl estradiol. In the tenidap group, however, the ethinyl estradiol Cmax increased significantly between menstrual cycles 1 and 2 (252.9-271.3 pg/ml; p = 0.02). No tenidap-related side effects occurred. Five women reported menstrual irregularities, which were attributed to the single dose of OCs. No one experienced significant changes in heart rate or blood pressure. These findings show no pharmacokinetic interaction in women receiving tenidap and the OC simultaneously. Thus, tenidap use should not reduce OC efficacy.