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1. Ranitidine interacts with liver microsomes from rats pretreated with different inducers of cytochrome P-450 to produce substrate difference optical spectra with a peak at 426-429 nm and a trough at 390-400 nm. 2. Cytochrome P-450 reduced with dithionite in the presence of ranitidine produced substrate difference spectra with a peak at 447 nm. 3. Ks values for the interaction of ranitidine with cytochrome P-450 (not reduced), calculated from double reciprocal plots, were in the range 1.4-2.8 mM. 4. The O-dealkylation of 7-ethoxycoumarin and of p-nitroanisole was inhibited by the presence of ranitidine and the inhibition was of a mixed type. Kii and Kis values were: for inhibition of 7-ethoxycoumarin dealkylation, 0.8 to 9 mM, and 0.16 to 0.67 mM, respectively; for inhibition of p-nitroanisole dealkylation, 5.8 to 13.7 mM, and 1 to 4.5 mM, respectively. 5. The I50 values for 7-ethoxycoumarin dealkylation was 1.8 mM and for p-nitroanisole dealkylation about 7.2 mM (microsomes from phenobarbital-pretreated rats). 6. The e.p.r. spectra of cytochrome P-450 from phenobarbital-pretreated rats, in the presence of ranitidine, reveal two types of interaction depending on the ranitidine concentration. At lower concentrations of ranitidine, a ligand exchange reaction with an oxygen atom is indicated, and at higher concentrations are with nitrogenous or thioether ligand of ranitidine.

Time of day of administration and the fat and caloric content of the accompanying meal had minimal overall effect on the pharmacokinetic properties and bioavailability of the pregabalin CR formulation.