Comparative drug elimination capacity in man‐glutethimide, amobarbital, antipyrine, and sulfinpyrazone

Abstract

The apparent elimination half-lifes were determined for 4 drugs that undergo hydroxylation in men. Glutethimide (500 mg), amobarbital sodium (130 mg), antipyrine (1.0 gm), and sulfinpyrazone (400 mg) were each taken orally by 10 healthy men at weekly intervals. When the half-lifes in these 10 individuals were compared, positive correlations were found among 3 out of 4 drugs: glutethimide-amobarbital (r 0.69, p < 0.05), glutethimide-sulfinpyrazone (r 0.64, p < 0.05), and amobarbital-sulfinpyrazone (r 0.87, p < 0.01). If these data are generally valid, it would mean, for example, that one could, from the sulfinpyrazone half-life in a given sub;ect, predict the amobarbital half-life of the same individual within about ± 7 hours (30% of average half-life, while the interindividual differences could be 300%). Antipyrine half-life was not correlated with the half-life of any of the other 3 drugs. The urinary levels of 6f3-hydroxycortisol were also determined in the same sub;ects and compared with the half-lifes of the 4 drugs. The correlation coefficients taken singly were not statistically significant, but they were all negative and collectively seem to indicate an expected trend.

A comparative study of antipyrine and lignocaine disposition in normal subjects and in patients treated with enzyme‐inducing drugs.

“…In previous studies, no significant relationship could be found between the halflife of antipyrine and the half-life of other drugs which are similarly metabolized by the mixed function oxidases, e.g. amylobarbitone, glutethimide, sulfinpyrazone, phenylbutazone, dicoumarol, aminopyrine, phenacetin, diazepam and quinine Davies, Thorgeirsson, Breckenridge & Orme, 1976;Kadar, Malsa, Endreyi, Johnson & Kalow, 1973;Vesell, Passananti, Greene & Page, 1971;Vesell & Page, 1968;Hepner, Vesell, Lipton, Harvey, Wilkinson & Schenker, 1977). In the above studies, however, elimination kinetics were generally compared in subjects with relatively homogeneous drug metabolizing capacity, such as normal volunteers selected from a uniform environment.…”

Enzyme Induction by Drugs

“…The drug most often used is antipyrine, and comparison of its plasma half-life in groups of subjects and in individuals before and after exposure to a drug has been valuable in assessing induction in man, and for investigating the genetic control of microsomal enzyme activity (Vessell and Page, 1969). On the other hand, the half-life of antipyrine does not always correlate well in an individual with the plasma half-lives of other drugs known to be metabolised by the microsomal detoxicating enzyme system (Kadar et al, 1973). It cannot be used to predict how an individual will respond to any other drug.…”

Pharmacokinetics of single doses of sulphinpyrazone and its major metabolites in plasma and urine.

“…Table 5 summarises the results of sigma minus plots of the urinary excretion of sulphinpyrazone and its sulphone and parahydroxy metabolites (the minimum correlation coefficient for these plots was 0.979). The renal clearance of unchanged sulphinpyrazone and the sulphone appear in (Kadar et al, 1973) and 3.5 h for ten normal subjects (Senczuk & Jodynis-Liebert, 1979), both estimates being made from studies of urinary elimination kinetics. Shorter half-lives, 2.2 and 2.7 h, were found in two normal males given radiolabelled sulphinpyrazone by Dieterle et al (1975).…”