‘Pavlovian’ Food Effect on the Enterohepatic Recirculation of Piroxicam

Polli, James E.; Bigora, Sian; Piscitelli, Deborah A.; Straughn, Arthur B.; Young, David

doi:10.1002/(sici)1099-081x(199610)17:7<635::aid-bdd981>3.3.co;2-w

Cited by 6 publications

(12 citation statements)

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“…Most plasma concentration–time curves exhibited two peaks after oral administration of meloxicam, with a small second peak occurring 10 to 12 h after administration. This result has also been reported previously for the disposition of piroxicam [22, 23] and meloxicam [24–27]. The AUC and the elimination half‐life of intravenous meloxicam are reduced by cholestyramine, indicating involvement of the entero‐hepatic or entero‐enteric circulation [28], which may explain the observed double peaks and prolonged absorption of meloxicam.…”

Section: Discussionsupporting

confidence: 88%

Effects of *CYP2C9**1/*13 on the pharmacokinetics and pharmacodynamics of meloxicam

Bae

Choi

Jang

et al. 2011

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Meloxicam is a substrate for the CYP2C9 and CYP3A4 enzymes. • We have previously reported that the frequency of the CYP2C9*1/*13 genotype in the Korean population is 1.1%. WHAT THIS STUDY ADDS • The CYP2C9*1/*13 genotype is associated with decreased metabolism and increased pharmacodynamic effects of meloxicam. • This is the first report that evaluates the in vivo effects of the CYP2C9*13 allele on the pharmacokinetics and pharmacodynamics of CYP2C9 substrates with a sufficient sample size. AIMS To determine the effects of the CYP2C9*1/*13 genotype on the pharmacokinetics and pharmacodynamics of meloxicam in Korean subjects. METHODS Meloxicam (15 mg) was orally administered to 21 healthy Korean volunteers with either the CYP2C9*1/*1 or the CYP2C9*1/*13 genotype. Plasma meloxicam concentrations were analysed by HPLC‐UV for 72 h after drug administration. The pharmacodynamic effects of meloxicam were determined by measuring TXB2 generated in blood. RESULTS The AUC(0,∞) and Cmax of meloxicam were 2.43‐ and 1.46‐fold higher in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group, respectively. The oral clearance of meloxicam was significantly lower in the CYP2C9*1/*13 group (37.9% of wild type) than in the CYP2C9*1/*1 group. The t1/2 of meloxicam was 1.84‐fold longer in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group. The rate of TXB2 production was significantly lower in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group. CONCLUSIONS The CYP2C9*1/*13 genotype is associated with decreased metabolism and increased pharmacodynamic effects of meloxicam.

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Section: Discussionsupporting

confidence: 88%

Effects of *CYP2C9**1/*13 on the pharmacokinetics and pharmacodynamics of meloxicam

Bae

Choi

Jang

et al. 2011

Brit J Clinical Pharma

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“…Indomethacin (Schneider et al ., 1990), piroxicam (Polli et al ., 1996), diclofenac (Schneider et al ., 1990) and sulindac (Verbeeck, 1988) have been reported to show an enterohepatic circulation in humans. Piroxicam undergoes enterohepatic circulation in beagle dogs (Polli et al ., 1996). In rats, an enterohepatic circulation occurs after the administration of ibuprofen (Dietzel et al ., 1990).…”

Section: Resultsmentioning

confidence: 70%

The oral bioavailability of ibuprofen enantiomers in broiler chickens

Vermeulen

Remon

2001

Vet Pharm & Therapeutics

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Doses of racemic ibuprofen ranging from 5 to 20 mg/kg body weight were administered intravenously (i.v.) and orally to broiler chickens and plasma concentration-time profiles for both ibuprofen enantiomers were determined. The absorption of ibuprofen was evaluated after a bolus administration of a commercially available suspension into the crop and proventriculus, respectively. An enterohepatic circulation as described for other nonsteroidal anti-inflammatory drugs (NSAIDs) in other species could be suggested for both enantiomers after i.v. and oral administration. Significantly higher area under the curve (AUC) values for S(+)-ibuprofen compared with R(-)-ibuprofen were collected after crop and proventriculus administration. Several factors could be responsible for the significant differences in AUC values between both enantiomers.

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“…In response to a meal, bile salts are released into the intestine. It has been reported that a Pavlovian‐type effect can cause the release of bile salts prior to eating the meal (Polli et al. , 1996) thus accounting for the second maximum concentration at 8 h. Thus, enterohepatic recycling may be contributing to the broad concentration profile observed.…”

Section: Discussionmentioning

confidence: 98%

Pharmacokinetic properties of toceranib phosphate (Palladia™, SU11654), a novel tyrosine kinase inhibitor, in laboratory dogs and dogs with mast cell tumors

Yancey

Merritt

Lesman

et al. 2010

Journal of Veterinary Pharmacology and Therapeutics

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Toceranib phosphate (Palladia, SU11654), an oral tyrosine-kinase inhibitor, is under investigation for the treatment of mast cell tumors in dogs. The pharmacokinetics of toceranib phosphate has been characterized in dogs. Means of the following pharmacokinetic parameters were estimated following a 1.0 mg/kg i.v. dose to laboratory beagles: plasma clearance of 1.45 L/kg/h, volume of distribution of 29.7 L/kg, and terminal half-life of 17.7 h. Following single oral doses of 3.25 mg/kg administered to laboratory beagles, mean C(max) estimates ranged from 68.6 ng/mL to 112 ng/mL with t(max) ranging from 5.3 h and 9.3 h postdose. Terminal half-life was estimated at 31 h. Oral bioavailability was 76.9%. There were no statistically significant (P > 0.05) differences with any pharmacokinetic parameter due to fed/fasted state or with time during 13 weeks of every-other-day dosing at 3.25 mg/kg. Toceranib concentrations were proportional with dose over the range of 2.0 to 6.0 mg/kg. The pharmacokinetics of toceranib in client-owned dogs of a variety of pure and mixed breeds with mast cell tumors was similar to that in healthy laboratory dogs. In summary, toceranib phosphate exhibited moderate clearance, a high volume of distribution, and a moderate elimination half-life. After a single oral dose at 3.25 mg/kg, the concentration vs. time curve showed broad, sustained exposure with measurable concentrations for more than 48 h. These pharmacokinetic parameters support every-other-day administration of toceranib phosphate at an initial dose of 3.25 mg/kg for the treatment of mast cell tumors in dogs.

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‘Pavlovian’ Food Effect on the Enterohepatic Recirculation of Piroxicam

Cited by 6 publications

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Effects of *CYP2C9**1/*13 on the pharmacokinetics and pharmacodynamics of meloxicam

Effects of *CYP2C9**1/*13 on the pharmacokinetics and pharmacodynamics of meloxicam

The oral bioavailability of ibuprofen enantiomers in broiler chickens

Pharmacokinetic properties of toceranib phosphate (Palladia™, SU11654), a novel tyrosine kinase inhibitor, in laboratory dogs and dogs with mast cell tumors

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‘Pavlovian’ Food Effect on the Enterohepatic Recirculation of Piroxicam

Cited by 6 publications

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Effects of CYP2C9*1/*13 on the pharmacokinetics and pharmacodynamics of meloxicam

Effects of CYP2C9*1/*13 on the pharmacokinetics and pharmacodynamics of meloxicam

The oral bioavailability of ibuprofen enantiomers in broiler chickens

Pharmacokinetic properties of toceranib phosphate (Palladia™, SU11654), a novel tyrosine kinase inhibitor, in laboratory dogs and dogs with mast cell tumors

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Product

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Effects of *CYP2C9**1/*13 on the pharmacokinetics and pharmacodynamics of meloxicam

Effects of *CYP2C9**1/*13 on the pharmacokinetics and pharmacodynamics of meloxicam