Pharmacokinetics of low-dose and high-dose buprenorphine in cats after rectal administration of different formulations

Objectives A prospective experimental study was performed in nine young healthy cats to investigate a pharmacokinetic profile and the clinical relevance of rectally administered buprenorphine. Rectal pH value was measured in all nine cats. Methods Blood was collected 15, 30, 60, 90, 120, 240 and 480 mins and 24 h after the rectal administration of a suppository and a gel at doses between 0.02 mg/kg and 0.1 mg/kg buprenorphine to determine the plasma concentration of buprenorphine. Rectal pH was measured with pH paper. Results Upon pharmacokinetic non-compartment analysis of high-dose buprenorphine (0.1 mg/kg), average maximal plasma concentration was found to be 1.13 ng/ml, time to maximal plasma concentration was 45 mins and area under the plasma concentration–time curve was 94.19 ng*min/ml, representing low but potential bioavailability. Mean residual time was 152.2 mins and the half-life was 92.6 mins. A wide range of plasma concentrations within the cohort was measured and two of the cats had to be excluded from statistical analysis owing to incomplete uptake. Vital parameters of all cats were considered to be normal but three of the cats showed mydriasis up to 8 h after application. After the administration of a low-dose suppository or a rectal gel (0.02 mg/kg) within pilot studies, no buprenorphine was detected in cat plasma. Rectal pH in all cats was between 7.7 and 8. Conclusions and relevance The rectal application of buprenorphine at a dose of 0.1 mg/kg revealed a potential but weak uptake in cats. Regarding effective concentrations in previous pharmacokinetic investigations, rectal administration is currently not recommended for good provision of opioid analgesia in cats. Pharmacological investigations of formulation and galenics in order to improve the rectal bioavailability of buprenorphine remain to be clarified before further dose-finding and pharmacokinetic/pharmacodynamic studies are performed.

Effects of Vitamin D Plus Calcium Supplements on Pharmacokinetics of Isoflavones in Thai Postmenopausal Women

The objective of this study was to determine the effects of vitamin D3plus calcium supplements (D3-calcium) on pharmacokinetics of isoflavones in Thai postmenopausal women. This study was an open-labeled, randomized three-phase crossover study. Twelve healthy subjects were randomized to receive one of the following regimens: (a) a single dose of isoflavones, (b) a single dose of isoflavones, and D3-calcium, or (c) continuous D3-calcium for 7 days followed by a single dose of isoflavones on the 8th day. After a washout period, subjects were switched to receive the 2 remaining regimens according to their randomized sequences. Blood samples were collected before dose and at specific time points until 32 hours after isoflavone administration. Plasma was treated with β-glucuronidase/sulfatase to hydrolyze glucuronide and sulfate conjugates of daidzein and genistein. Plasma concentrations of daidzein and genistein were determined by high performance liquid chromatography. The estimated pharmacokinetic parameters of isoflavones were time to maximal plasma concentration (Tmax), maximal plasma concentration (Cmax), half-life (t1/2) and area under the plasma concentration-time curve (AUC).Tmaxof daidzein and genistein after regimen B was significantly longer than that of regimen A. Other pharmacokinetic parameters of daidzein and genistein obtained following the three regimens were not significantly different.

Influence of bran on bioavailability of chloramphenicol administered orally to pigs

The present study was undertaken to determine if bran added to a fiber-free diet (milk) would modify the absorption of orally administered chloramphenicol (cmp) compared with that observed on a standard concentrates diet in pig. The plasma chloramphenicol level was maximal (0.47 ± 0.26 μg/mL), 3.5 h after a meal of concentrates containing 8 g of chloramphenicol palmitate; this highest concentration represented only 30% of that observed 12 h after a meal of substituted milk and 14% of the maximal plasma concentration of chloramphenicol detected 14 h after a milk meal when supplemented with bran (100 g). Over 24 h, the plasma availability of chloramphenicol with the three tested diets represented, respectively, 11.4% (concentrates), 17.2% (milk), and 74.1% (milk + bran) of that obtained for intravenous administration; similar oral–caecal transit times were observed for these three diets. It was concluded that the presence of bran in the regimen strongly increases the intestinal absorption of chloramphenicol palmitate, with the lowest rate of absorption on standard concentrates, and it is tempting to speculate that this increase is due to a more rapid intestinal hydrolysis by an increased pancreatic lipase activity on bran.