INCREASED SYSTEMIC AVAILABILITY OF LOPERAMIDE AFTER ORAL-ADMINISTRATION OF LOPERAMIDE AND LOPERAMIDE OXIDE WITH COTRIMOXAZOLE

1 The effects of concurrent administration of cotrimoxazole on the pla sma concentration-time profiles of loperamide and its oxide were inves tigated in two separate studies in healthy male volunteers. Cotrimoxaz ole (960 mg, twice daily) was administered for 24 h before and 48 h af ter an oral dose of loperamide oxide (4 mg) or loperamide (4 mg). 2 Co administration of cotrimoxazole with loperamide oxide did not alter th e t(max), C-max and AUC of loperamide oxide, whereas the C-max (0.32 /- 0.14 ng ml(-1) without cotrimoxazole; 0.45 +/- 0.18 ng ml(-1) with cotrimoxazole; P < 0.05) and AUC (8.13 +/- 1.91 ng ml(-1) h without co trimoxazole; 12.50 +/- 4.60 ng ml(-1) h with cotrimoxazole; P < 0.005) of loperamide were significantly increased. 3 Coadministration of cot rimoxazole with loperamide significantly increased the C-max (0.74 +/- 0.22 ng ml(-1) without cotrimoxazole; 1.49 +/- 0.81 ng ml(-1) with co trimoxazole; P < 0.01) and AUC (13.40 +/- 3.80 ng ml(-1) h without cot rimoxazole; 25.30 +/- 11.10 ng ml(-1) h with cotrimoxazole; P < 0.005) of loperamide, whilst its t(max) and t(1/2,z) were not significantly altered. 4 The increase in loperamide AUC, following coadministration of either loperamide oxide or loperamide with cotrimoxazole, may be du e to reduced first pass metabolism of loperamide.