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Pharmacokinetics of phenylbutazone in healthy subjects after oral administration of single and multiple doses.

Plasma concentration profiles were studied after single and oral doses of phenylbutazone of 100, 300, and 600 mg in cachets to six healthy volunteers. The pharmacokinetics of phenylbutazone can be described by a two-compartment open model. The drug is absorbed rapidly and distributed partially into an extravascular compartment; about one-third remains in the plasma. The mean elimination half-life was 77 hr (54-99 hr), and there was a linear relationship between the dose and the area under the plasma concentration curve. In a multiple-dose study, six healthy volunteers received 150 mg of phenylbutazone in cachets twice daily every 11-13 hr for 17 days. A steady state was reached after approximately 200 hr of chronic treatment. The resultant steady-state plasma concentration were about four times higher than the peak concentration produced by a single 150-mg dose. The half-lives corresponding to the apparent elimination rate constant for the first and last administrations did not differ in each subject. The theoretical minimum concentrations are higher than the pseudosteady state reached during chronic treatment.