Pharmacokinetics of isoniazid in Wistar rats exposed to ethanol

Abstract Tuberculosis treatment consists of a drug combination, where isoniazid is the core drug and alcoholism is a factor highly related to poor patient compliance with the therapy. CYP2E1 is an enzyme involved both in the metabolism of ethanol and in the formation of hepatotoxic compounds during the metabolism of isoniazid. The shared metabolism pathway accounts for the possibility of pharmacokinetic interaction in cases of concomitant alcohol use during tuberculosis treatment. The aim of this study was to evaluate the effect of repeated exposure of Wistar rats (males, 250 g, n=6) to ethanol on the pharmacokinetics of a single dose of isoniazid in combination with pyrazinamide and rifampicin (100 mg/kg, 350 mg/kg and 100 mg/kg, respectively). An animal group received the combination of drugs and ethanol and was compared to a control group, which received the combination of drugs without exposure to ethanol. The plasma concentrations of isoniazid were determined by a UHPLC/UV bioanalytical method that was previously validated. Biochemical markers of liver function were measured to assess potential damage. A lower elimination half-life of isoniazid was observed in the ethanol group than in the control group (t1/2 0.91 h versus 1.34 h). There was no evidence of hepatotoxicity through the biomarker enzymes evaluated. The results allow us to infer that although there are no biochemical changes related to liver damage, there is a slight influence of ethanol exposure on the pharmacokinetic profile of isoniazid. This change may have a relevant impact on the efficacy of isoniazid in the outcome of tuberculosis treatment.

Pharmacokinetic interaction between sunitinib and ramipril in rats / 中国药科大学学报

The purpose of this study was to investigate the pharmacokinetic interaction between sunitinib and ramipril in rats. Eighteen male SD rats were divided into three groups, with each group being assigned to orally receive sunitinib, ramipril, sunitinib and ramipril, respectively, for ten days. Blood samples were collected at dif-ferent times after first-day and tenth-day administration. The concentrations of ramiprilat and sunitinib in rat plasma were determined by LC/MS/MS and the pharmacokinetic parameters were calculated and statistically analyzed. Compared with the administration of ramipril alone, after a single-dose combined administration, tmax of ramiprilat decreased significantly and t1/2 prolonged, while AUC0-∞ remained unchanged. These results indicated that the ab-sorption rate of ramiprilat increased and the elimination rate decreased, but total absorption degree was not changed. After multiple-dose administrations, CL of ramiprilat decreased and AUC0-∞ increased obviously. It sug-gested that accumulation of ramiprilat occurred in body and the drug elimination became slower. No obvious difference of sunitinib pharmacokinetic behavior was found when it was given in combination with ramipril after a single-dose administration or multiple-dose administration. Sunitinib decreased the elimination of ramiprilat after co-administration in company with drug accumulation in body after multiple-dose co-administration. The study showed that there were pharmacokinetic interactions between sunitinib and ramipril in SD rats.

The Pharmacokinetic Interaction and Therapeutic Plasma Concentration of Oxcarvazepine / 대한간질학회지

PURPOSE: Oxcarbazepine (OXC) is chemically related to carbamazepine (CBZ). OZC exerts less liver enzyme induction than CBZ and is completely metabolized by reduction to the active metabolite, 10, 11-dihydro-10-hydroxy-5H-dibenzo (b,f) azepine-5-carboxamide (MHD). It was known that OXC had no significant pharmacokinetic interactions with other antiepileptic drugs. But it is not thoroughly studied yet because of short duration of clinical application. We investigated whether the plasma concentration of OXC metabolite (MHD) is changed by valproic acid compared with OXC monotherapy and studied the correlation of the dose of OXC with the plasma concentration of its active metabolite (MHD). METHODS: The patient with OXC monotherapy (19 cases) and patients with OXC and valproic acid(16 cases) were incluses. We analyzed the level of its metabolites MHD by HPLC RESULTS: The plasma concerntration of MHD in OXC monotherapy is 15.5+/-3.2 microgram/ml and that of the MHD in polytherapy with valproic acid is 16.4+/-3.4 microgram/ml at the same dose of OXC. The plasma concentration of MHD is ranged from 7.4 microgram/ml at 600 mg/day of OXC to 27.0 microgram/ml at 1800 mg/day of OXC and highly correlated with OXC dose per body weight (r=0.72-84). CONCLUSION: There is no significant change or difference of MHD plasma concentraion between OXC monotherapy and polytherapy with valproic acid at the same dose of OXC. THe plasma concentration of MHD is highly correlated with OXC dose per body weight.

Influence of Sijunzi Decoction on the pharmacokinetics of Levofloxacin in experimental spleen dificiency rat / 中成药

AIM: To investigate the influence of Sijunzi Decoction(Radix et Rhizoma ginseng,Rhizoma atractylodis macrocephalae,poria,Radix et Rhizoma glycyrrhizae) on the pharmacokinetics of Levofloxacin(LVFX) in rats with deficiency of spleen. METHODS: Twenty-four rats were randomly divided into four groups: NS(normal rats given 0.9% saline solution),NS+SJZT(normal rats given 0.9% saline solution and Sijunzi Decoction),R(rats pretreated with Reserpine) and R+SJZT(rats pretreated with Reserpine and then cured with Sijunzi Decoction).After a single oral administration of LVFX 20 mg/kg,blood samples were collected at different intervals.The concentrations of LVFX plasma were determined by HPLC.Pharmacokinetic parameters were determined from the plasma concentration-time data. RESULTS: Reserpine led to the syndromes similar to the deficiency of spleen,a traditional Chinese medicine syndrome.The pharmacokinetic parameters of LVFX in NS,NS+SJZT,R and R+SJZT groups were as follows: AUC_((0-∞))=(8.55 ?0.99),(7.41?1.39),(4.68?0.95) and(7.89?1.41)mg/(L?h),respectively and C_(max)=(3.31?0.63),(2.38?1.15),(1.29?0.45) and(3.35?1.15) mg/L,respectively.Compared with the parameters of LVFX in NS group,Reserpine markedly decreased AUC_((0-∞)) and C_(max) of LVFX(P