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AIM: To investigate the effects and quantitative relations of co-administering probenecid OF different dosages on pharmacokinetics of cefaclor in rabbits and approach the possible mechanisms involved as well. METHODS: Monitor plasma and urine cefaclor concentrations. 24 male rabbits were randomly divided into 4 groups by Cefaclor 50 mg·kg-1,Cefaclor50 mg·kg-1+Probenecid 100 mg·kg-1,Cefaclor 50 mg·kg-1+Probenecid 250 mg·kg-1 and Cefaclor 50 mg·kg-1+Probenecid 625 mg·kg-1.Blood and urine samples were collected according to the regular time schedule after intragastric administration. The concentration of cefaclor in blood and urine were determined by HPLC. Pharmacokinetic parameters were calculated by DAS (Drug and Statistical) software. Measur plasma protein-binding rate of cefaclor. The experimental groups and drug dosage were same as described above. The blood sample was drawn at 1 hour after administration,and the protein-binding rate of cefaclor was determined by equilibrium dialysis. RESULTS: Within the dosages of probenecid ranged from 0-250 mg·kg-1,T1/2ka,Tmax,Cmax and AUC of cefaclor increased in accordance with increasing dosage of co-administering probenecid while CL/F and Vd/F were decreased(P＜0.01); However,when the dosage of co-administering probenecid was 625 mg·kg-1,Cmax of cefaclor strikingly decreased(P＜0.01),while AUC and CL/F maintained at the levels of those with probenecid250 mg·kg-1.In this experiment, urinary excretive peak time of cefaclor in its prototype pos tponed gradually,biological half life prolonged and urinary excretive accumulation percentage decreased obviously(P＜0.01).To the dosages of probenecid ranging from 0-250 mg·kg-1,protein-binding rate of cefaclor decreased notably(P＜0.01)going with increasing dosages of co-administration probenecid; While the dosage of co-administration probenecid reached 625 mg·kg-1,the protein-binding rate of cefaclor corresponded to that of cefaclor 50 mg·kg-1 without probenecid (P＜0.01).CONCLUSION: Co-administering probenecid can strikingly change pharmacokinetics of cefaclor and the influential degree of pharmacokinetics parameters is dependent on dosages of probenecid used in the experiment. Biological half life prolongs and urinary excretive accumulation percentage of cefaclor decreases obviously.
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0.05) . CONCLUSION: Ampicillin and probenecid capsules are of bioe-quiavailability.
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AIM: To observe the effects of proben-ecid of different doses on pharmacokinetics of cefaclor and to provide the basis of their co-adiministration. METHODS: 30 rabbits were randomly divided into 5 groups: Cef 50 mg?kg -1, Cef 50 mg?kg -1+Pro 50 mg?kg -1,Cef 50 mg?kg -1+Pro 100 mg?kg -1,Cef 50 mg?kg -1+Pro 200 mg?kg -1,Cef 25 mg?kg -1+Pro 100 mg?kg -1. The blood samples were drawn from thigh vein after IG and the concentrations of cefaclor were determined by HPLC. Pharmacokinetics parameters were calculated by NDST procedure. RESULTS: In groups with Cef 50 mg?kg -1, C max and AUC of cefaclor increased, and Vd/F and Cl/F decreased progressively with the adding probenecid. There was no significant difference between Cef 25 mg+Pro 100 mg and Cef 50 mg?kg -1 in each parameter except Cl/F. CONCLUSION: Probenecid can remarkably alter the pharmacokinetics of cefaclor and the magnitude of the effects of probenecid is dependent on its dose in this trial. Cef 25 mg?kg -1 with Pro 100 mg?kg -1 can reach the same blood concentration as Cef 50 mg?kg -1 alone.
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We encountered a case of renal hypouricemia and absorptive hypercalciuria. Although renal hypouricemia is asymptomatic as usual, it is rarely complicated with acute renal failure and urolithiasis. A 43-year-old man had hypouricemia (serum uric acid, 0.6-1.0mg/dl) with an increased renal uric acid clearance (69.4ml/min), hypercalciuria (367.2mg/day). In present case, there was no response of uric acid excretion to either pyrazinamide or probenecid and hypercalciuria disappeared after calcium restriction diet. These results suggest that the present case had the defect of both pre-and postsecretory reabsorption of uric acid and absorptive hypercalciuria.
Subject(s)
Adult , Humans , Acute Kidney Injury , Calcium , Diet , Hypercalciuria , Probenecid , Pyrazinamide , Uric Acid , UrolithiasisABSTRACT
A marked low concentration of serum uric acid(0.7-1.2mg/dl) was detected in a 14-year-old boy with recurrent episodes of gross hematuria. The hypouricemia accompanied with a markedly increased urinary clearance of uric acid (32.6-56.0ml/min), which was only minimally changed after both the administration of pyrazinamide, and inhibitor of the renal tubular secretion of uric acid, and the administration of probenecid, and inhibitor of the renal tubular reabsorption of uric acid. Other renal tubular functions were normal. There were no other family members with hypouricemia. Thies is the first case report of isolated renal hypouricemia due to presecretory reabsorption defect of uric acid in the renal proximal tubule in Korea. And renal hypouricemia should be included in the diagnosis of hematuria.
Subject(s)
Adolescent , Humans , Male , Diagnosis , Hematuria , Korea , Probenecid , Pyrazinamide , Uric AcidABSTRACT
Objective To develop a high performance liquid chromatography(HPLC) method to determine the concentration of ampicillin and probenecid in human plasma.Methods A Symmetry ShieldTM RP18 column(5 ?m,150 mm?3.9 mm)was used.The mobile phases were 0.068 mol/L KH_2PO_4(pH 3.0)∶acetonitre(92∶8,V/V)for ampicillin,H_2O∶acetonitrile∶1 mol/L KH_2PO_4∶1 mol/L acetic acid(59.5∶39.8∶0.62∶0.062,V/V,0.15% triethylamine added to reach pH 2.76) for probenecid.The detective wavelength were at 254 nm for probenecid and 210 nm for ampicillin.Results The calibration curves obtained were linear in the range of 0.625-20 ?g/ml (r=0.999 9) of probenecid and 1.25-40 ?g/ml of ampicillin.Conclusion This analysis method is simple,sensitive and rapid,suitable for studying pharmacokinetics of ampicillin and probenecid.