Pharmacokinetics ketoprofen

Skeith, K.J. Russell, A.S. Jamah, F. Ketoprofen pharmacokinetics in the elderly influence of rheumatic disease, renal function, and dose. J. Clin. Pharmacol. 1993, 33, 1052 1059. 

Etman MA, Ismail FA, Nada AH. Effect of metoclopramide on ketoprofen pharmacokinetics in man. IntJPharmaceutics ( 992) 88,433-5. 

The proper dose of ketoprofen for an optimized zero-order model to obtain the desired drug level pattern to remain in the therapeutic range for 12 h (twice-a-day formulation) was estimated from drug pharmacokinetic parameters [6] by conventional equations [3] on the basis of a one-compartment open model and was found to be 1 lOmg. 

Ketoprofen is a propionic acid derivative that inhibits both COX (nonselectively) and lipoxygenase. Its pharmacokinetic characteristics are given in Table 36-1. Concurrent administration of probenecid elevates ketoprofen levels and prolongs its plasma half-life. 

Ketoprofen is an arylpropionic acid derivative that contains a single asymmetrical carbon atom and therefore exists in two enantiomeric forms that differ in their pharmacokinetic and pharmacodynamic properties (96). It is available for veterinary use in products containing the racemic mixture, and is indicated for treatment of respiratory infections in sheep and mastitis-metritis-agalactia syndrome in the sow. The recommended dosage is 3 mg/kg bw in a single injection (97). 

Jamali, F., Brocks, D.R. Clinical pharmacokinetics of ketoprofen and its enantiomers. Clin. Pharmacokinet. 1990, 19, 197-217. 

The influence of a single dose of omeprazole on the pharmacokinetics of enteric-coated ketoprofen tablets was tested [65], There was no significant difference with or without single-dose omeprazole administration for the systemic bioavailability of the ketoprofen products. A trend in higher plasma concentrations with omeprazole indicates a possibility of drug release from enteric-coated products at potentially elevated stomach pH values. 

S. A. Qureshi, G. Caille, Y. Lacasse, I. J. McGilveray, Pharmacokinetics of two enteric coated ketoprofen products in humans with or without coadministration of omeprazole and comparison with dissolution findings, Pharm Res 11(11) 1669-1672 (1994). 

F. Jamali, N. N. Singh, E M. Easutto, R. T. Courts, and A. S. Russell, "Pharmacokinetics of ibuprofen enantiomers in man following oral administration of tablets with different absorption rates," Pharm. Res., 5 40-43 (1988), R. T. Foster, E Jamali, A. S. Russell, and S. R. AlbeUa, "Pharmacokinetics of ketoprofen enantiomers in young and elderly arthritic patients following single and multiple doses," ]. Pharm. ScL, 77 191-195 (1988). 

Foster, R.T. Jamah, F. Russell, A.S. Alballa, S.R. Pharmacokinetics of ketoprofen enantiomers in young and elderly arthritic patients following single and multiple doses. J. Pharm. Sci. 1988, 77 (3), 191-195. 

Table 14 Pharmacokinetic parameters describing disposition of S(+)- and R(—)-enantiomers after intravenous administration of racemic ketoprofen (KTP) to horses (n = 6) and sheep (n = 6)...

Landoni, M.F. Lees, P. Influence of formulation on the pharmacokinetics and bioavailability of racemic ketoprofen in horses. J. Vet. Pharmacol. Ther. 1995c, 18, 446-450. 

Mauleon, D. Mis, R. Ginesta, J. Ortega, E. Vilageliu, J. Basi, N. Carganico, G. Pharmacokinetics of ketoprofen enantiomers in monkeys following single and multiple oral administration. Chirality 1994, 6, 537-542. 

Fillastre JP, Leroy A, Borsa-Lebas F, Etienne I, Gy C, Humbert G. Effects of ketoprofen (NSAID) on the pharmacokinetics of pefloxacin and ofloxacin in healthy volunteers. Drugs Exp Clin Res 1992 18(ll-12) 487-92. 

Advenier C, Roux A, Gobert C, Massias P,VaraquauxO, Flouvat B. Pharmacokinetics of ketoprofen in the elderly. Brit J Clin Pharmacol 1983 16 65-70. 

Thyss A, Milano G, Kubar J, Namer M, Schneider M. Clinical and pharmacokinetic evidence of a life-threatening interaction between methotrexate and ketoprofen. Lancet, 1986,1 256-258. 

In general, NSAIDs share a number of different pharmacokinetic properties. For example, most, but not all, have relatively short plasma half-lives. Meclofenamic acid and ketoprofen, for example, have plasma half-lives of l-2h in the horse (Owens et al 1995a, Snow et al 1981). Phenylbutazone has a more variable plasma half-life but it is usually determined to be less than 8h (Lees Higgins 1985). In contrast, the plasma half-life of carprofen is between 18 and 21 h in the horse (Lees et al 1994, McKellar et al 1991). 

In the presence of inflammation, the pharmacokinetics of NSAIDs may be altered. For example, in one study comparing with normal horses, the clearance and of phenylbutazone were increased in horses with experimentally induced inflammatory loci (Mills et al 1996). Horses with experimentally induced inflammation also cleared ketoprofen faster than normal horses (Owens et al 1995a). 

The pharmacokinetics of ketoprofen has also been studied in neonatal foals. Neonatal foals clear ketoprofen more slowly and have a larger than adult horses (VVilcke et al 1998). It is important to note that these studies were carried out in healthy normal foals and that pharmacokinetic parameters could be altered in sick or compromised foals. Nevertheless, the results of these studies suggest that the initial dose of ketoprofen may need to be increased in neonatal foals and the subsequent dosing interval increased in order to produce plasma concentrations comparable to adults (Wilcke et al 1998). 

Vedaprofen is a propionic acid derivative that, like carprofen and ketoprofen, exists as two enantiomers with different pharmacokinetic profiles in the horse. For example, the plasma disposition of S(-t-)-vedaprofen is characterized by a very rapid decline with a plasma half-life of less than 1 h while R(-)-vedaprofen has a more prolonged elimination phase with a plasma half-life of over 2h (Lees et al 1999). Both enantiomers also accumulate in and exhibit a delayed elimination from inflammatory exudates. In horses, vedaprofen appears to be slightly selective for the COXl enzyme. For example, the median effective concentration for inhibition of serum TXB2 production, which is assumed to be a reflection of COXl activity, was much lower than that for inhibition of inflammatory infiltrate PGE2 production, which is assumed to be a reflection of COX2 activity. Although the results of these studies are promising, there are no published data on the clinical effectiveness and safety of vedaprofen in horses. 

Equine Veterinary Journal 27 247-256 Landoni M F, Lees P 1995b Influence of formulation on the pharmacokinetics and bioavallabllity of racemic ketoprofen in horses. Journal of Veterinary Pharmacology and Therapeutics 18 446-450 Landoni M F, Foot R, Frean S et al 1996 Effects of flunixin, tolfenamic acid, fl(-) and S(+) ketoprofen on the response of equine synoviocytes to lipopolysaccharide stimulation. Equine Veterinary Journal 28 468-475... 

Pharmacokinetics of ketoprofen in healthy horses and horses with acute synovitis. Journal of Veterinary Pharmacology and Therapeutics 18 187-195 Owens J G, Kamerling S G, Stanton S R et al 1995b Effects of ketoprofen and phenylbutazone on chronic hoof pain and lameness in the horse. Equine Veterinary Journal 27 296-300... 

Pharmacokinetics of ketoprofen after multiple i.v. doses to mares. Journal of Veterinary Pharmacology and Therapeutics 18 108-116 Schary W L, Lewis R J, Rowland M 1975... 

Wiicke J R, Crisman M V, Scarratt W K et al 1998 Pharmacokinetics of ketoprofen in healthy foals less than 24 hours old. American Journal of Veterinary Research 59 290-292... 

Example Ibuprofen (Motrin, Advil, Nuprin) naproxen (Naprosyn) (Aleve is a similar OTC drug) Oxaprozin (Daypro) ketoprofen (Orudis). Route PO Pregnancy category B Pharmacokinetic Absorbed from the GI tract, metabolized in the liver and primarily excreted in urine ... 

Jaussaud, P., Bellon, C., Besse, S., Courtot, D. Delatour, P. (1993) Enantioselective pharmacokinetics of ketoprofen in horses. Journal of Veterinary Pharmacology and Therapeutics, 16, 373-376. 

Landoni, M.F. Lees, P. (1996) Pharmacokinetics and pharmacodynamics of ketoprofen enantiomers in the horse. Journal of Veterinary Pharmacology and Therapeutics, 19, 466-474. 

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