Pregnancy is associated with profound changes in renal hemodynamics and electrolyte handling. Relaxin, a hormone secreted by the corpus luteum, has been shown to induce pregnancy-like increases in renal blood flow and glomerular filtration rate (GFR) and alter osmoregulation in nonpregnant female and male rats. However, its effects on renal electrolyte handling are unknown. Accordingly, the influence of short (2 h)- and long-term (7 day) infusion of relaxin on renal function was determined in the male rat. Short term infusion of recombinant human relaxin (rhRLX) at 4 microg.h(-1).100 g body wt(-1) induced a significant increase in effective renal blood flow (ERBF) within 45 min, which peaked at 2 h of infusion (vehicle, n = 6, 2.1 +/- 0.4 vs. rhRLX, n = 7, 8.1 +/- 1.1 ml.min(-1).100 g body wt(-1), P < 0.01). GFR and urinary excretion of electrolytes were unaffected. After a 7-day infusion of rhRLX at 4 microg/h, ERBF (1.4 +/- 0.2 vs. 2.5 +/- 0.4 ml.min(-1).100 g body wt(-1), P < 0.05), urine flow rate (3.1 +/- 0.3 vs. 4.3 +/- 0.4 microl.min(-1).100 g body wt(-1), P < 0.05) and urinary sodium excretion (0.8 +/- 0.1 vs. 1.2 +/- 0.1 micromol.min(-1).100 g body wt(-1), P < 0.05) were significantly higher; plasma osmolality and sodium concentrations were lower in rhRLX-treated rats. These data show that long-term relaxin infusion induces a natriuresis and diuresis in the male rat. The mechanisms involved are unclear, but they do not involve changes in plasma aldosterone or atrial natriuretic peptide concentrations.

Relaxin causes renal hyperfiltration, natriuresis, and diuresis in male rats. This study determined the effect of recombinant human relaxin (rhRLX) on renal function in the female rat. After 7 days of rhRLX treatment (0.4 microg/h) urinary excretion of sodium and chloride were significantly lower in the rhRLX-treated group, but urine flow rate was not different from that in controls. Quantitative PCR showed that the RXFP1 receptor was expressed in both the renal cortex and medulla; immuno-localization revealed expression in the proximal tubule and inner medullary collecting ducts. These data show that relaxin elicits pregnancy-like changes in renal function in the female rat.

The Pharmacokinetic profile of thiamphenicol glycinate HCl was studied in male goats following single intravenous and intramuscular administration of 30 mg kg-1 b.wt. Thiamphenicol concentration in serum was determined by microbiological assay using Bacillus subtilis (ATCC 6633) as test organism. After intravenous injection the serum thiamphenicol concentration time course was found to obey two-compartment open model with distribution (t 0.5(α)) and elimination (t 0.5(β)) half lives of 0.0.06 ± 0.003 and 1.20 + 0.163 h., respectively. Total body clearance (Cl B) and steady state volume of distribution (Vd ss) were 1.025 ± 0.04 L kg-1 h-1 and 0.51± 0.010 L kg-1 ., respectively. After intramuscular administration the observed mean peak serum concentration (C max) was 6.89 ± 0.052 µg ml-1 achieved after maximum time (t max) of 1.53 ± 0.08 hour post-injection.The systemic bioavailability after intramuscular was 87.61 %. The plasma protein binding percent was 13.3%.

No abstract

Concurrent administration of drugs may alter their pharmacokinetic parameters, so; investigation to what extent bromhexine hydrochloride affects the pharmacokinetic behavior of tilmicosin was our aim of this work. Ten broiler chickens were classified into two groups as follow, the first one (tilmicosin group) was given single oral dose of tilmicosin (20 mg/kg.b.wt.) while the 2nd (pre-treated group) was given single oral dose of bromhexine hydrochloride (1 mg/kg.b.wt.) followed by single oral dose of tilmicosin (20 mg/kg.b.wt.) one hour later. The serum concentration of tilmicosin was measured using High Pressure Liquid Chromatography (HPLC) method. The results revealed that the mean serum concentrations of tilmicosin were significantly lower in pre-treated group when compared with tilmicosin alone group at the corresponding time intervals. Pharmacokinetic parameters were significantly differed (p<0.001) between both groups. The maximum serum concentration were (Cmax0.70±0.02, 0.81±0.04µg/ml), achieved at Tmax of (tmax 0.89±0.16, and 2.10±0.06h), absorption half-life (t0.5ab) of 0.16±0.08, and 0.37±0.01 hour, area under curve (AUC) of 12.96±0.42 and 16.73±0.42µg.h/ml) in tilmicosin-bromhexine and tilmicosin alone groups respectively. In conclusion, based on the obtained pharmacokinetic parameters, these findings showed that bromhexine accelerates the tilmicosin penetration into body tissues, achieving higher and faster concentrations than when given tilmicosin alone.