摘要:

This study compares pharmacokinetic parameters and colonic tissue concentrations of cyclosporine administered by olive‐oil or water‐retention enemas with conventional intravenous (IV) and oral dosing. Five medical students were enrolled in a prospective crossover study. All subjects received a single dose of cyclosporine on four separate occasions, once orally, once as an olive‐oil enema, once as a water enema, and once IV. Cyclosporine concentration was measured in blood and in colonic tissue obtained by flexible sigmoidoscopy. Bioavailability was 18 ± 7% (mean ± SDJ for the oral dose and was unmeasurable for the oil and water enemas. The concentration of cyclosporine in colon tissue was 32,443 ± 17,251 ng/g (mean ± SDJ for the IV dose, 2797 ± 1812 ng/g for the oral dose, 21,727 ± 14,090 ng/g for the oil enema, and 25,318 ± 30,408 ng/g for the water enema. The authors conclude that the bioavailability of cyclosporine, and thus the systemic absorption after administration by a retention enema, is negligible. The colonic tissue concentration of cyclosporine after IV or rectal administration via an enema is tenfold higher than that for oral dosing. These findings suggest that cyclosporine‐retention enemas produce high distal colonic tissue concentrations with negligible systemic absorption after a single dose in healthy subjects and should be evaluated as treatment for patients with left‐sided colitis. Because cyclosporine administered by the IV route provided sharply higher colonic tissue concentrations than those seen with oral therapy, pulse IV cyclosporine should be tried for patients with severe ile

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01890.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

This randomized, double‐blind study investigated the effect of ciprostene, a stable epoprostenol (prostacyclin) analog in patients with peripheral vascular disease (PVD) characterized by ischemic ulcers. A total of 211 patients (106 ciprostene, 105 placebo) received IV infusions of ciprostene (120 ng/kg/min in 8‐hour daily infusions for 7 days) or placebo. The two groups were comparable with regard to demographic data. Only 45% of the patients receiving ciprostene and 55% of the placebo patients completed the trial. The groups were similar in frequency of amputations, vascular surgery, and development of new ulcers. Among those who completed the trials an insignificantly higher percentage of patients receiving ciprostene had all ulcers heal completely. The reduction of ulcer size by at least 50% was higher in the ciprostene‐treated group at month 4(P = .005).Both ciprostene and placebo reduced the severity of a patient's rest pain. There was no difference in the ankle brachial index between the groups. Ciprostene induced a higher incidence of headache, nausea, and flushing during infusion when compared with the placebo group. The results confirmed inherent problems with studies in PVD, namely, scarcity of patients with ischemic ulcers, inclusion of severely ill patients leading to a high dropout rate, and a high placebo effect. Good tolerance and safety of ciprostene was documented in this patient population, and the therapeutic benefit was limited to partial reduction of ulcer size. Selection of patients with less advanced disease and a longer infusion of ciprostene may improve the clinical benefit of this

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01891.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Eight patients with arthritis and knee effusions received 13 doses of a single 800‐mg ibuprofen tablet every 8 hours. Serum and synovial fluid samples were obtained after the first and last doses and assayed for the R(−) and S(+) enantiomers of ibuprofen by a stereospecific assay. Since only S(+)‐ibuprofen inhibits cyclo‐oxygenase, a description of the time course of this isomer in synovial fluid is needed for the development of suitable pharmacodynamic models. The isomers were significantly different with respect to peak concentrations and areas under the concentration—time curves (AUC) in synovial fluid levels. No significant accumulation of either isomer was observed in serum or synovial fluid levels between the first and the last doses. The steady‐state concentration of both isomers fluctuated less in synovial fluid than in plasma, and the synovial fluid concentrations of the S(+) isomer were about twice that of the R(−) isomer. The mean synovial albumin concentration was about 60% of the serum albumin concentration, and the steady‐state isomer AUC values in synovial fluid were significantly correlated with the corresponding serum values after the differences between the two fluids with respect to albumin concentration were corrected. The authors conclude that binding of the isomers to albumin and the serum—synovial fluid albumin ratio controls the steady‐state distribution of the ibuprofen isomers into synovial fluid. The ramifications of these findings in the development of satisfactory concentration—response relati

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1991.tb01892.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY