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Biomedical subjects

R Girkin

Publications and source records attributed to R Girkin.

6 recordsLinked to original sources
PubMed1983

Biotransformation of lofexidine in humans.

1. Concentrations of unchanged drug and patterns of radioactive components in urine have been determined by h.p.l.c. following single oral doses of [14C]lofexidine hydrochloride (0.32 mg) to six human subjects. 2. A mean of 12% of the administered dose was excreted in urine as unchanged lofexidine, but the wide range (5-20% dose) indicated significant intersubject variation in the extent of biotransformation. This drug would appear to be metabolized more extensively than the related anti-hypertensive agent, clonidine. 3. The principal metabolite of lofexidine was 2,6-dichlorophenol, which was apparently excreted in urine as two O-glucuronic acid conjugates. The same two metabolites were also the main 14C components circulating in plasma at peak 14C concn. Formation of the phenol from lofexidine probably involved direct O-dealkylation rather than stepwise degradation of the side-chain. 4. Patterns of 3H components in the urine of rats and dogs after oral administration of [3H]lofexidine hydrochloride (0.1 mg/kg) were generally similar to those in human urine.

Adult↗
PubMed1980

The metabolic fate of tizoprolique acid in baboons.

1. After oral administration of the anti-lipolytic drug [14C]tizoprolique acid (2-propyl-5-carboxyl[4-14C]thiazole), to baboons (60 mg/kg), the radioactivity was well absorbed and rapidly excreted. During 6 and 24 h respectively, 60 +/- 25% (S.D.) and 90 +/- 2% were excreted in the urine. 2. Plasma concn. of 14C reached a max. (182 +/- 65, range 85-221 micrograms equiv./ml) at 1-1.5 h after an oral dose, and declined rapidly with an apparent half-life of about 0.5 h. A mean of 77 +/- 7% of the 14C in peak plasma samples was bound to plasma proteins, somewhat less than that of [14C]tizoprolique acid (84 +/- 5%). 3. Tissue concn. of 14 C were highest in an animal killed at 0.5 h after an oral dose, but were lower than those in plasma in all tissues examined except the kidneys. 4. The major metabolite of tizoprolique acid was its glycine conjugate, which accounted for about 80% dose excreted in the 24 h urine. About 2% dose was excreted as unchanged drug. About 70% and 20% respectively of plasma 14C were associated with the unchanged drug and its glycine conjugate during the period 15 min to 4 h after dosing.

Absorption↗
PubMedDate not supplied

Metabolic fate of the beta-blocker 14C-bupranolol in humans, dogs, and rhesus monkeys.

An oral dose of 14C-bupranolol hydrochloride was well absorbed by humans (100 mg), dogs (1 mg/kg), and rhesus monkeys (1 mg/kg). These species excreted 87.8 and 3.5%, 81.1 and 13.6%, and 92.9 ad 5.0% of the 14C-dose in urine and feces, respectively, mainly in 12 or 24 hr. Mean plasma levels of 14C, which appeared to be almost entirely associated with a single metabolite, peaked at 1 hr in humans (1.6 micrograms-equiv./ml) and dogs (1.6 micrograms-/ml) and at 2 hr in monkeys (0.8 micrograms-equiv./ml). Concentrations initially declined with similar half-lives (about 1.5 hr) in all three species. Biliary excretion of 14C occurred in the animal species in which also peak plasma 14C levels exceeded those in most tissues. Unchanged bupranolol was not detected in plasma; the peak plasma and urinary 14C was mainly associated (greater than 90% in humans) with a metabolite produced by oxidation of the aromatic ring methyl group of bupranolol to a carboxyl group.

Absorption↗