Rectal administration pharmacokinetics

Pharmacokinetics Readily absorbed from the G1 tract following PO administration. Well absorbed following rectal administration. Protein binding 70%-80%. Metabolized inliveranderythrocytestotheactivemetabolite,trichloroet Hanoi, which may be further metabolized to inactive metabolites. Excreted in urine. Half-life 7-10 hr (trichloroethanol). 

Pharmacokinetics Slowly and incompletely absorbed from the GI tract rapidly and extensively absorbed after rectal administration. Protein binding greater than 90%. Undergoes extensive first-pass metabolism in the liver to active metabolite. Eliminated in feces by the biliary system. Half-life 21 hr. 

Pharmacokinetic properties Meptazinol has poor oral bioavailability due to extensive first-pass metabolism. Systemic availability is improved after rectal administration. Peak plasma concentrations are reached 30 min after rectal or intramuscular administration and plasma half-life is about 2 h. Plasma protein binding is low ( 30%). Meptazinole is extensively metabolized in the gut and liver mainly to the glucuronide derivative. Only about 10% is excreted unmetabolised in the faeces (Franklin, 1988). 

Pharmacokinetic and Pharmacodynamic Parameters for Insulin and Glucose Following Rectal Administration of Insulin, SNAP, and Carboxy-PTIO... 

Kowari, K., et al. 2002. Pharmacokinetics and pharmacodynamics of human chorionic gonadotropin (hCG) after rectal administration of hollow-type suppositories containing hCG. Biol Pharm Bull 25 678. 

Pharmacokinetics Phenylbutazone is rapidly and completely absorbed after oral or rectal administration. Oxyphenbutazone is an active metabolite and contributes to the activity of the parent drug. Like most of the other NSAIDs, phenylbutazone is extensively bound to plasma proteins. This property causes displace-... 

Pharmacokinetics. Absorption of xanthines after oral or rectal administration varies with the preparation used. It is generally extensive (> 95%). Caffeine metabolism varies much between individuals (t/ 2-12 h). Xanthines are metabolised (more than 90%) by numerous mixed function oxidase enzymes, and xanthine oxidase. (For further details on theophylline, see Asthma.)... 

Pharmacokinetics. Metronidazole is well absorbed after oral or rectal administration and distributed to achieve sufficient concentration to eradicate infection in liver, gut wall and pelvic tissues. It is eliminated in the urine, partly imchanged and partly as metabolites. The t) is 8 h. 

Example Promethazine hydrochloride (Phenergan) Route PO/IM/ Pregnancy category C Rectal/TV Pharmacokinetic Well absorbed from GI tract, after IM administration Widely distributed metabolized in liver excreted in urine PB 60%-90%... 

Example Bisacodyl (Dulcolax) Route PO/Rectal Pregnancy category C Pharmacokinetic Minimal absorption following PO, rectal administration. Absorbed drug excreted in urine remainder eliminated in feces. 

Cook, G., Papich, M.G., Roberts, M.C. Bowman, K.F. (1997) Pharmacokinetics of cisapride in horses after intravenous and rectal administration. American Journal of Veterinary Research, 58, 1427-1430. 

Van Peer, A., Embrechts, L., Woestenborgs, R. et al Pharmacokinetics of cisapride and its bioavailability after oral and rectal administration in six healthy male volunteers. FDA Clinical Pharmacology Biopharmaceutics Review (s), pp. 27-28, see http //www.fda.gov/... 

A characteristic of artemisinin and its related endoperoxide drugs is the rapid clearance of parasites in the blood in almost 48 horns. Titulaer obtained pharmacokinetic data for the oral, intramuscular and rectal administration of artemisinin to volunteers [132], Rapid but incomplete absorption of artemisinin given orally occurs in humans with a mean absorption time of... 

Schmitt, M. Guentert, T.W. Biopharmaceutical evaluation of ketoprofen following intravenous, oral, and rectal administration in dogs. J.Pharm.Sci., 1990, 79, 614-616 [plasma dog naproxen (IS) pharmacokinetics]... 

For morphine, hydromorphone, and oxymorphone, rectal administration is an alternate route for patients unable to take oral medications, but equianalgesic doses may differ from oral and parenteral doses because of pharmacokinetic differences. 

Rectal administration of an active substance can be justified only if adequate data are available about the release from the dosage form and the absorption from the rectum. Without such a support rectal administration of an active substance should be discouraged. Tables with data from biopharmaceutical and pharmacokinetic research on rectally administered active substances are available from literature [5a]. 

AG De Boer, F Moolenaar, LGJ de Leede, DD Breimer. Rectal drug administration clinical pharmacokinetic considerations. Clin Pharmacokinet 7 285-311, 1982. 

Rectal bioavailability and pharmacokinetics. Serenoa repens extract, administered rectally to 12 healthy male volunteers at a dose of 640 mg/person, produced the mean maximum concentration in plasma of nearly 2.60 (Xg/mL approx 3 hours after administration, with mean value for the area under the curve AUC 10 (Xg/hour/mL. The bioavailability and pharmacokinetic profile were similar to those observed after oral administration. T j occurred approx 1 hour later, and plasma concentration 8 hours after drug administration was still quantified. The drug tolerability was good, and no adverse effect was observed ". Serenoa repens capsules, administered orally at a dose of 160 mg four times daily or rectally 640 mg daily for 30 days to 60 patients with BPH, produced no significant differences in diminu-... 

Van Hoogdalem, E.J., A.G. De Boer, and D.D. Breimer. 1991. Pharmacokinetics of rectal drug administration, Part I. General considereations and clinical applications of centrally acting drugs. Clin Pharmacokinet 21 11. 

De Boer, A.G., et al. 1982. Rectal drug administration Clinical pharmacokinetic consideration. Clin Pharmacokinet 7 285. 

Watanabe, Y., et al. 1996. Pharmacokinetics and pharmacodynamics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) after administration of a rectal dosage vehicle. Biol Pharm Bull 19 1059. 

Various characteristics of the molecule influence its chances of reaching its target receptor since they influence the nature and extent of the body s effect on it. A drug s pharmacokinetic profile therefore determines the extent of the drug s opportunity to exert its pharmacodynamic effect. While there are various routes for human drug administration (oral rectal intravenous, subcutaneous, intramuscular, and intra-arterial injections topical and direct inhalation into the lungs), the most common for small-molecule drugs is oral administration, and discussions in the first part of this chapter therefore focus on oral administration. (In contrast, biopharmaceuticals are typically administered by injection, often directly into the bloodstream.)... 

Strenkoski-Nix LC, Ermer J, DeCleene S, et al. (2000) Pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories and oral syrup to healthy subjects. Am J Health-Syst Pharm 57 1499-1505. 

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