Evaluation of the bioavailability and pharmacokinetics of two extended-release theophylline formulations in dogs

Abstract

Results of these single-dose studies indicated that administration of the specific brand of extended-release theophylline tablets or capsules used in this study at a dosage of 10 mg x kg(-1), PO, every 12 hours would maintain plasma concentrations within the desired therapeutic range (10 to 20 microg x mL(-1)) in healthy dogs.

Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia

“…The pharmacokinetics of intravenous, intraperitoneal or subcutaneous AMP administration best fitted the two-compartment model, with rapid distribution and slow elimination. Titres of plasma theophylline peak within 8 min of injection and the normal elimination half-life of AMP ranges from 8 to 14 h, while the bioavailability of AMP is 80-95% in humans [23], dogs [24], cats [25], pigs [26] and chickens [25]. Although the pharmacokinetics and bioavailability of AMP have not been previously assessed in naked mole rats, these are likely to be similar to published values in other species.…”

Pharmacokinetics of a modified, compounded theophylline product in dogs

“…It has been hypothesized that the short t 1/2,β of rapid release theophylline initially reported (McKiernan et al, ) may actually be due to genetic homogeneity of drug metabolizing enzymes among the purpose‐bred animals used in that study rather than the drug formulation (Bach et al, ; KuKanich & Nauss ). Pharmacokinetics of intravenous theophylline in Greyhounds and in a mixed patient population have demonstrated longer terminal t 1/2 (8.4–9.2 hr) compared to purpose‐bred animals (5.7 hr), supporting a difference in clearance rather than absorption of different formulations (Bach et al, ; KuKanich & Nauss , McKiernan et al, ). The long t 1/2 of intravenous aminophylline in our mixed population was 7.52 ± 1.18 hr, providing further evidence for this theory.…”

“…It should be noted that theophylline products marketed as slow release or extended release in humans generally do not have extended‐release properties in dogs (Bach et al, ; Koritz et al, ). This requires demonstration of a slower absorption versus elimination rate (i.e.…”

“…For oral administration, the MCT product was compounded for each dog at a dose of approximately 10 mg/kg. This dose was selected based on previously published studies evaluating the extended‐release theophylline products in dogs (Bach et al, ). Dogs were allowed free access to water and were fed their normal diet twice daily.…”

Factors Influencing the Gastric Residence of Dosage Forms in Dogs

“…Human–canine differences in oral bioavailability have been at least in part attributed to this difference in crushing force for a several products including cyclandelate capsules,54 indomethacin capsules,55 and griseofulvin tablets 56. When extended‐release theophylline formulations intended for human use were administered to dogs (Theochron tablets and TheoCap capsules, Inwood Laboratories, Inwood, NY), there was little evidence of an extended‐release profile 57. The mean canine terminal half‐life for IV theophylline, the oral extended‐release tablets, and oral extended‐release capsules were all similar (8.4, 10.9, and 12.7 h, respectively).…”