Pharmacokinetic comparison of oral and local action transcutaneous flurbiprofen in healthy volunteers.

Flurbiprofen is a propionic acid-derived non-steroidal anti-inflammatory drug (NSAID) used widely in the treatment of rheumatism and non-arthritic pain. The pharmacokinetics of topically and orally administered flurbiprofen were compared in a two-part, open study involving healthy adult volunteers. In the first (cross-over) part of the study, 12 Caucasians were randomized to receive either a single oral dose of 50 mg flurbiprofen or a single topical application of a novel 40 mg flurbiprofen-containing patch on the right wrist for 12 h. In the second part of the study, each subject applied a flurbiprofen-containing patch twice daily to the same wrist for 7 days. Plasma concentrations of flurbiprofen and urinary concentrations of the NSAID and its metabolites were measured by high-performance liquid chromatography assay, to enable comparison of the pharmacokinetic parameters for delivery of the drug by both routes. Maximum concentrations of the NSAID in plasma (Cmax) were much lower after a single application of the topical 40 mg flurbiprofen patch than after a single oral dose of 50 mg of the NSAID (mean +/- SD: 43 +/- 16 ng/ml versus 5999 +/- 1300 ng/ml, respectively). After repeated application of the topical patch, Cmax increased only slightly to 103 +/- 57 ng/ml. The mean relative bioavailability of flurbiprofen from the patch was 3.5 +/- 1.7%, calculated from plasma area under the curve data and 4.4 +/- 2.8% from urinary excretion data.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical ionisation mass fragmentographic measurement of dothiepin plasma concentrations following a single oral dose in man.

A method is described for the measurement of the antidepressant drug dothiepin in human plasma. The procedure involves the addition of deuterodothiepin as an internal standard, extraction and measurement by chemical ionisation mass fragmentography. The minimum measurable concentration of 0.5 ng/ml enabled the pharmacokinetics of dothiepin in man to be studied after a single oral dose of 75 mg of dothiepin hydrochloride. Unlike other tricyclic antidepressants the apparent half-life of elimination (approximately 24 h) showed very little intersubject variation. However, the apparent volume of distribution was much more variable and could account for the wide range of steady state concentrations which have been found in patients taking dothiepin.

Bioavailability of chlorpropamide.

1. The serum profiles of chlorpropamide obtained following single doses of two tablet preparations and from a suspension formulation have been compared in healthy volunteers. The amounts of chlorpropamide absorbed from the three formulations were similar but the drug was absorbed more rapidly from the suspension than from either tablet formulation. There was a small but therapeutically insignificant difference in the rate of absorption of the drug from the two tablets. 2. Changes in blood glucose concentrations were found to be related to the drug serum profile characteristics of the formulations.

Steady-state serum concentrations of dothiepin and northiaden after two dosage regimens of dothiepin hydrochloride (Prothiaden).

Five healthy volunteers took part in a crossover study which examined the serum concentrations of dothiepin and northiaden after a 25 mg three times a day and a 75 mg once a day dosage regimen of Prothiaden. The inter-individual variation of serum levels was large after either schedule which is to be expected with this group of drugs. The minimum steady-state level of dothiepin tended to be lower after the single daily dose, but the differences were small and not statistically significant. The approximate maximum steady-state levels of dothiepin showed large intra-and inter-subject variation and no obvious trend. The values of the desmethylated metabolite, norhiaden, tended to follow the dothiepin concentrations but were lower than the parent drug. Average steady-state levels tended, with one exception, to be very similar after both regimens with no evidence with no evidence fo any trend when comparing the two regiments. The study showed that the two regimens yielded similar steady-state serum concentrations both of drug and metabolite but inter-individual differences were large.

Concentrations of flurbiprofen in serum and synovial fluid from patients with active rheumatoid disease: some preliminary observations.

In 3 patients with active rheumatoid disease, concentrations of flurbiprofen of approximately 2 microgram per ml were achieved in synovial fluid 3 hours after a single oral dose of flurbiprofen (100 mg). The highest concentrations were seen between 3 and 9 hours after administration of the dose. The concentration of flurbiprofen in synovial fluid seemed to fall more slowly than in the circulation, but more extensive data would be needed to confirm this. In all 3 patients the drug was absorbed rapidly into the circulation, the highest serum concentrations of 7 microgram to 9 microgram per ml being seen in the first blood sample withdrawn 1.5 hours after administration of the dose. Serum concentrations fell with a mean apparent half-life of approximately 3 hours.

Serum concentrations of flurbiprofen in rheumatoid patients receiving flurbiprofen over long periods of time.

Serum concentrations of flurbiprofen were measured following single oral doses of 50 mg to 200 mg in patients who previously had received flurbiprofen over long periods of time. The apparent elimination half-lives in groups of patients who received different doses were not significantly different from each other nor from the value previously obtained in a group of healthy volunteers given a single oral dose of 50 mg. Areas under serum concentration versus time curves were linearly related to dose over the range of doses examined. The results indicate that the pharmacokinetics of flurbiprofen are not significantly dose-dependent over the range of doses studied and that administration of relatively high doses of flurbiprofen over long periods of time neither induces nor inhibits flurbiprofen metabolism.