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  • Author or Editor: Tania E. Perez x
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Abstract

OBJECTIVE

Develop a cytochrome P450 (CYP) phenotyping cocktail for dogs using specific substrates for hepatic P450 enzymes CYP2B11, CYP2D15, and CYP3A12 and determine whether alternative sampling methods (saliva and urine) or single time point samples could be used instead of multiple blood sampling.

ANIMALS

12 healthy client-owned dogs (8 females and 4 males) from February 2019 to May 2019.

METHODS

In a randomized crossover study, dogs received oral administration of the probe drug bupropion (75 mg), dextromethorphan (30 mg), or omeprazole (40 mg) alone or as a 3-drug combination (Program in Individualized Medicine [PrIMe] cocktail) to evaluate simultaneous phenotyping of CYP2B11, CYP2D15, and CYP3A12. Pharmacokinetic profiles for the probe drugs and metabolites were determined using plasma, saliva, and urine. Dogs received probe drugs alone or combined. Pharmacokinetic profiles up to 6 hours postdose for the probe drugs and metabolites were determined using plasma, saliva, and urine.

RESULTS

The PrIMe cocktail was well tolerated. There was no statistically significant interaction between the probe drugs when administered together. Single time point plasma metabolic ratios at 4 hours postdose for all probe drugs strongly correlated with the corresponding area under the plasma concentration-versus-time curve (AUC) ratios. Saliva AUC metabolic ratios for CYP3A12 and CYP2D15 and 6-hour urine for CYP2B11 and CYP2D15 were correlated with plasma AUC ratios.

CONCLUSIONS

The PrIMe cocktail can be used for simultaneous CYP phenotyping using plasma 4-hour single time point sample metabolic ratios. Saliva and urine sampling are suitable for specific CYPs.

CLINICAL RELEVANCE

The PrIMe cocktail has potential as a useful tool in dogs to detect clinically important CYP-mediated drug-drug interactions, identify novel pharmacogenes, determine the drug-metabolizing phenotype of individual dogs, aid in individualized dose selection, and evaluate the effects of various physiological states on drug metabolism.

Open access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine the intraoperative and postoperative analgesic efficacy of intratesticular or epidural injection of analgesics for dogs undergoing castration.

Design—Randomized controlled trial.

Animals—51 healthy male dogs.

Procedures—Dogs were assigned to a control group that received analgesics systemically (hydromorphone [0.1 mg/kg {0.045 mg/lb}, IM] and carprofen [4.4 mg/kg {2.0 mg/lb}, SC]; n = 17), an epidural treatment group that received analgesics systemically and morphine (0.1 mg/kg) epidurally (17), or an intratesticular treatment group that received analgesics systemically and bupivacaine (0.5 mg/kg [0.23 mg/lb]/testis) intratesticularly (17). Dogs were anesthetized and castrated by veterinary students. Responses to surgical stimulation were monitored intraoperatively, and treatments were administered as required. Pain scores were assigned via a modified Glasgow composite pain scale after surgery. Serum cortisol concentrations were determined at various times. Rescue analgesia included fentanyl (intraoperatively) and hydromorphone (postoperatively).

Results—Compared with control dogs, dogs in the intratesticular bupivacaine and epidural morphine treatment groups received significantly fewer doses of fentanyl intraoperatively (11, 1, and 5 doses, respectively) and hydromorphone postoperatively (14, 7, and 3 doses, respectively) and had significantly lower postoperative pain scores (mean ± SEM score at first assessment time, 71 ± 0.5, 4.8 ± 0.2, and 4.5 ± 0.4, respectively). At 15 minutes after removal of the testes, serum cortisol concentrations were significantly higher than they were immediately prior to surgery for all groups and values for the intratesticular bupivacaine treatment group were significantly lower versus the other 2 groups.

Conclusions and Clinical Relevance—Intratesticular or epidural injection of analgesics improved perioperative analgesia for dogs undergoing castration.

Full access
in Journal of the American Veterinary Medical Association