Oxazepam pharmacokinetics in thyroid disease.

Abstract

1 The pharmacokinetics of oxazepam, a drug mainly eliminated by a single step glucuronidation reaction, were studied in seven hyperthyroid and six hypothyroid patients before and after treatment.2. Oxazepam elimination half-life was shorter and apparent oral clearance higher in untreated hyperthyroid patients than after treatment. There was no significant change in oxazepam elimination in hypothyroid subjects.3 Time to peak concentration (tmax) was reduced in the hyperthyroid state. Hypothyroidism had no significant effect on tmax* 4 Serum bilirubin concentration was lower in the patients while hyperthyroid before treatment than when euthyroid and also lower than in the hypothyroid patients. There was no significant correlation between serum bilirubin concentrations and oxazepam elimination. 5 These results suggest that glucuronyl transferase activity is increased in hyperthyroidism but is not altered in most patients with hypothyroidism. The extent of increase in glucuronyl transferase activity is similar to that produced by enzyme inducing drugs.

Pharmacokinetics and pharmacodynamics of oxazepam and metabolism of paracetamol in severe hypothyroidism.

“…Thus, the suggestion of Scott et al (1984) that the elimination of oxazepam may proceed at a slower rate in more severe degrees of hypothyroidism is confirmed. Our patients were characterized by routine thyroid laboratory tests as suffering from longstanding and advanced hypothyroidism.…”

“…Glucuronidation, a ances (Forfar et al, 1980). Oxazepam tended to *Present address and correspondence: Dr J. Sonne, Department of Internal Medicine and Gastroenterology, Herlev University Hospital, DK-2730 Herlev, Denmark. be eliminated at a slower rate in more severely hypothyroid patients (Scott et al, 1984).…”

Propylthiouracil Disposition in Older Hypothyroid Patients

“…Although data are fragmentary, a major pathway for PTU metabolism in man and in rats in volves conjugation with glucuronic acid [Kampmann and Mulholm-Hansen, 1981;Sitar and Thornhill, 1972]. Thus, our obser vation is consistent with the findings for ox azepam and acetaminophen disposition, two other drugs with major metabolic pathways involving conjugation and for which no im pairment in metabolism has been demon strated in hypothyroidism [Forfar et al, 1980;Scott et al, 1984], It should be remem bered that Vd and ty, determine Clp (Clp = (Vd X 0.693)/ti/j). When Vd and lv, both change in the same direction, as occurred in the present study, it is possible to have a minimal effect on Clp, even though the other pharmacokinetic parameters change by a substantial degree.…”

Does a selective 5‐hydroxytryptamine antagonist (ICI 169, 369) lower blood pressure in hypertensive patients?

“…system. The small change in bilirubin concentration was of the same magnitude as has been shown with hepatic enzyme induction (Scott et al, 1976) and hyperthyroidism (Scott et al, 1984). This raises the possibility that ICI 169, 369 could be inducing bilirubin glucuronyl transferase.…”