Bolus Oral Administration Research Articles

Effect of sustained release bolus oral administration on body condition change, blood parameters, and uterine health in primiparous cows under heat stress.

The transition period is very stressful for primiparous cows due to their first calving experience and will be more challenging if it occurs under heat stress conditions. Heat stress reduces the feed intake of dairy cows. Therefore, it reduces the consumption of minerals and vitamins. Oral administration of boluses through the provision of mineral-vitamin compounds can reduce metabolic abnormalities after calving. The present study aimed to evaluate effect of sustained-release bolus on body condition score (BCS) change, serum metabolites, uterine health, and reproductive status in primiparous cows. Heifers were selected at the beginning of the close-up period (n = 60, BCS = 3.35 ± 0.12). There were 2 experimental treatments at the time of calving: (1) heifers without bolus oral administration (H - Bo, n = 30); (2) heifers with bolus oral administration (H + Bo, n = 30). The results showed that although the rate of BCS loss was lower in the group receiving bolus, the effect of bolus was not significant. The effect of bolus on blood level of glucose, non-esterified fatty acids (NEFA), and beta-hydroxybutyrate (BHBA) was not significant; however, the highest concentration of albumin (P = 0.05) was observed in the H + Bo group on day 42 after calving. The concentration of aspartate transaminase (AST) tended to increase (P = 0.06) on day 14 after calving and entire the study. Total antioxidant capacity (TAC) was affected (P < 0.05) by bolus throughout the period of study, and the highest (P < 0.05) concentration of glutathione peroxidase (GPX) and superoxide dismutase (SOD) was observed in H + Bo group on day 42 after calving. The H + Bo group had the lowest (P < 0.05) vaginal discharge score (VDS). In general, oral administration of the sustained-release bolus in heifers significantly affected the antioxidant factors and uterine health, as well as had positive effects on liver function, body condition, and reproduction status.

Idiosyncratic liver injury induced by bolus combination treatment with emodin and 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucopyranoside in rats.

Polygoni Multiflori Radix (PMR) is a commonly used traditional Chinese medicine in clinical practice, while adverse effects of hepatotoxicity related to PMR have been frequently reported. The clinical case reports indicated that PMR hepatotoxicity could occur under both overdose medication/long-term exposure and low doses with short-duration (idiosyncratic) conditions. The combination treatment with emodin and 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG), two major PMR components, was reported to contribute to PMR hepatotoxicity after long-term treatment. However, the role of the combination treatment of these two components in PMR-induced idiosyncratic liver injury has not been clearly clarified. In this study, the LPS-mediated inflammatory stress model rats were adopted to explore the idiosyncratic liver injury induced by the bolus combination treatment with emodin and TSG. After a bolus oral administration with TSG (165 mg/kg), emodin (5 mg/kg) or their combination in both normal and LPS-mediated inflammatory stress model rats, the systemic/hepatic concentrations of emodin, emodin glucuronides and bile acids were determined; the hepatotoxicity assessments were conducted via monitoring histopathological changes and liver injury biomarkers (ALT and AST). Moreover, the protein expressions of bile acid homeostasis- and apoptosis-related proteins were examined. No liver damage was observed in the normal rats after a bolus dose with the individual or combination treatment, while the bolus combination treatment with emodin and TSG induced liver injury in the LPS-mediated inflammatory stress model rats, evidenced by the elevated plasma levels of alanine aminotransferase (∼66%) and aspartate aminotransferase (∼72%) accompanied by severe inflammatory cell infiltration and apoptotic hepatocytes in liver tissue. Moreover, such combination treatment at a bolus dose in the LPS-mediated inflammatory stress model rats could significantly elevate the hepatic TBA levels by about 45% via up-regulating the hepatic protein expression levels of bile acid synthesis enzymes and inhibiting that of bile acid efflux transporters and the expression levels of apoptosis-related proteins. Our study for the first time proved the major contribution of the combination treatment with emodin and TSG in PMR-induced idiosyncratic liver injury.

Pharmacokinetics of marbofloxacin, after one bolus oral administration in buffaloes calves: Preliminary study.

Buffalo breeding system has a great economic importance in South-America, principally in marginal or sub-tropical lands. The therapeutic recommendations applied to a single ruminant species are extrapolated to others but important differences among those were recognized. Marbofloxacin bolus is indicated in the treatment of neonatal gastroenteritis caused by Escherichia coli, in calves (25-50kg). The aim of this study was determined the pharmacokinetic behaviour of marbofloxacin after oral administration, as bolus, following the label approved recommendations to cattle. One bolus (50 mg) was administered in two clinically healthy buffaloes (two days-old, 48-50kg). Plasma concentrations of the marbofloxacin were determined by a HPLC/u.v. method. After oral administration, the values obtained were: tmax=0.5-6h, Cmax= 1.19-0.04μg/mL, AUCt=1.57-0.38μg·h/mL and MRTt= 3.34-6.92h, for calves 1 and 2 respectively. Fluoroquinolones act by concentration dependant killing mechanism, so high plasma concentration initially is important. For this reason, the recommended dose of 1mg/kg is inadequate in buffaloes.

Improved lipid lowering activity of bezafibrate following continuous gastrointestinal administration: pharmacodynamic rationale for sustained release preparation of the drug.

To evaluate the role of different routes and modes of administration of bezafibrate (BZF) on its hypolipidemic activity. We hypothesize that the major sites of BZF action are located presystemically as in other "gastrointestinal (GI) drugs." Thus, continuous administration of the drug to the GI tract is expected to augment its efficacy and provides a rationale for an oral sustained release preparation of the drug. The hypothesis was investigated in three experimentally induced-hyperlipidemia rat models. Models A and B were based on cholesterol-enriched diets and Model C on induced acute hyperlipidemia by triton 225 mg/kg. The pharmacokinetics and the pharmacodynamics of the drug following various modes of administration were examined. In all cases, continuous administration of the drug into the duodenum (IGI) at a dose of 30 mg/kg/day for 3 days (Models A and B) or over 18 hr (Model C) reduced significantly both total cholesterol and triglycerides levels and elevated HDL cholesterol levels in comparison to bolus oral administration of the same dose, as well as in comparison to equivalent intravenous infusion (Model C). Infusion of the drug directly into the portal vein produced an equivalent activity to IGI administration. The pharmacokinetic study showed 100% oral bioavailability, good colonic absorption properties and an indication for an enterohepatic cycle. The results confirm that BZF has a first pass hepatic pharmacodynamic effect. Administration of BZF in a slow release matrix tablet to the rats produced the same magnitude of effect as IGI administration, thus proving the pharmacodynamic rationale for this mode of administration for GI drugs.

Metabolism and pharmacokinetics of 1-(2′-hydroxyethyl)- and 1-(3′-hydroxypropyl)-2-ethyl-3-hydroxypyridin-4-ones in the rat

The urinary recovery (p.o.) and pharmacokinetics (i.v. and p.o.) of two compounds from the 1-hydroxyalkyl-3-hydroxypyridin-4-one series. 1-(2'-hydroxyethyl)-2-ethyl-3-hydroxypyridine-4-one (CP102) and 1-(3'-hydroxypropyl)-2-ethyl-3-hydroxypyridin-4-one (CP106) were studied in the rat. The pharmacokinetics of the 1-carboxyethyl metabolite (CP110) of CP106 was also studied (i.v.). CP102 was not metabolised to any considerable extent with 68.4 +/- 12.2% of the administered dose recovered unchanged in rat urine. In contrast, CP106 undergoes extensive phase I metabolism to form the 1-carboxyalkyl metabolite which accounted for 56.4 +/- 11% of the administered dose with 22.0 +/- 1.0% as unchanged drug. Intravenous and oral pharmacokinetics of CP102 and CP106 were studied in the rat at 450 mumols/kg. The AUCs of CP102 and CP106 after bolus i.v. infusion were 458 +/- 38 and 171 +/- 20 mumols/l.h. The AUC values after bolus oral administration were 318 +/- 46 and 77 +/- 18 mumols/l.h, respectively, with corresponding bioavailabilities (F) of 0.69 and 0.45. The Cmax of CP102 and CP106 were 142 +/- 25 and 70 +/- 15 mumols/l with Tmax values of 0.75 +/- 0.15 and 0.50 +/- 0.10 h, respectively. The CL, MRT and Vdss of CP102 was 1.00 +/- 0.09 l/kg/h, 0.92 +/- 0.04 h and 0.91 +/- 0.05 l/kg, respectively. The corresponding pharmacokinetic parameters for CP106 were 2.64 +/- 0.20 l/kg/h, 0.42 +/- 0.12 h and 1.12 +/- 0.26 l/kg, respectively. Renal clearance (CLR) of CP102 and CP106 were 1.00 +/- 0.18 l/kg and 1.27 +/- 0.31 l/kg respectively. The pharmacokinetics of CP110, which was conducted by the i.v. route only at a dose of 450 mumols/kg, had an AUC of 289 +/- 46 mumols/l.h, CL of 1.56 +/- 0.29 l/kg/h, MRT of 0.25 +/- 0.09 h and Vdss of 0.40 +/- 0.13 l/kg, respectively.