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• W2092279927 abstract "It is believed that acute pain suppresses nervus vagus, thereby, influencing gastrointestinal secretion and motility, which are the two factors that are necessary for disintegration and dissolution of solid dosage forms. We studied the pharmacokinetics of meloxicam and the effect of vagal suppression on the oral bioavailability and bioequivalence using a marketed (Brand) and a fast dissolving (FD) formulation. In simulated gastric juice, FD was disintegrated in 30 s and released 30% of its meloxicam in 15 min and 60% in 2 h. Brand was disintegrated in 4.5 min with a dissolution rate of 5.6% in 30 min that stayed plateau for the 2 h experiment time. To suppress the vagus nerve, intraperitoneal injection of 20 mg/kg propantheline 1 and 2 h before meloxicam administration was used. Meloxicam (0.9 mg/kg) was administered to both control and vagally suppressed rats i.v. (n = 4–6/group) as well as orally in a paired random fashion as broken pieces of Brand or FD tablets (n = 7/ group). Serial (0–48 h) blood samples were collected for pharmacokinetic and bioavailability studies. Relative bioavailability was measured according to a method in use for bioequivalence assessments. Systemic pharmacokinetics of meloxicam was not affected by vagal suppression. Absolute bioavailability of meloxicam, based on 0–48 h measurement, was >0.68 regardless of the type of formulation and treatment. Vagal suppression, however, significantly reduced AUC0–24 (μg h mL−1) for Brand (control, 58.8 ± 22.0 vs treated, 22.1 ± 9.7) but not for FD (control, 63.5 ± 17.9 vs treated, 64.6 ± 8.9) indicating a reduced absorption rate for the former. The peak time for Brand was also significantly delayed by over 20 h for Brand and not for FD. Relative bioavailability was confirmed between FD and Brand that were in control but not in the vagally suppressed rats, indicating a disease-dependent bioequivalence. The effect of vagal suppression on the drug absorption rate can be obviated if the disintegration and dissolution become independent of gastrointestinal motility and secretion." @default.
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• W2092279927 date "2008-11-01" @default.
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• W2092279927 title "Pharmacokinetics of meloxicam administered as regular and fast dissolving formulations to the rat: Influence of gastrointestinal dysfunction on the relative bioavailability of two formulations" @default.
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• W2092279927 doi "https://doi.org/10.1016/j.ejpb.2008.07.013" @default.
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