摘要:

AbstractFurosemide solution was orally administered to 21 healthy adult males to determine dose proportionality over the dose range used and the reproducibility of disposition following a repeated dose. Furosemide solution was given in doses of 20, 40, and 80mg, with the 40 mg dose repeated once. Blood was collected for 12 hours post‐dose and urine for 24 hours. The maximum plasma concentrations resulting from 20, 40, and 80mg doses were significantly different (p<0.05). Dose normalized maximum concentrations for the 20 and 80 mg doses were significantly different (p<0.05). Mean time to Cpmaxwas 50 minutes, with no differences observed among doses. Plasma AUCs were significantly different (p<0.05) for 20, 40, and 80mg. Dose normalized AUCs were not significantly different. Mean amounts of furosemide in urine (Xu) were 9.62, 16.7, and 32.0 mg for the 20, 40, and 80 mg doses, respectively. These amounts were significantly different (p<0. 05); dose normalized amounts were not significantly different. Renal clearances of furosemide following the three doses were not significantly different. Regressions of Cpmax, AUC andXuon dose were significant. There were no significant differences in Cpmax,tmax, AUC orXufor 40 mg given on two separate days. Renal clearance of furosemide was statistically different for 40mg given on two separate days, but the difference was not clinically significant. The pharmacokinetics of furosemide are linear over the dosage range studied. Furosemide 40 mg given on two separate days results in similar disposition parameter

ISSN:0142-2782    

DOI:10.1002/bdd.2510060202

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractIsosorbide 2,5‐dinitrate and its pharmacologically active metabolites, isosorbide 2‐nitrate and isosorbide 5‐nitrate, in plasma accumulated to the predicted steady‐state after five consecutive oral doses of sustained‐release tablets containing 40 mg isosorbide dinitrate at 12‐h intervals and after five consecutive oral doses of reference standard‐release tablets containing 20 mg at 6‐h intervals to 12 subjects in a crossover study. The comparative bioavailability of isosorbide dinitrate, isosorbide 2‐nitrate and isosorbide 5‐nitrate from the sustained‐release tablet was 110 per cent (p>0.05), 89 per cent (p>0.05), and 89 per cent (p<0.05), respectively, of that from the reference standard‐release tablet. The isosorbide dinitrate plasma level data were the more variable, as expected for a drug of low systemic availability subject to extensive first‐pass elimination. The posterior probability that the true bioavailability of isosorbide dinitrate was included within the usually accepted limits of 80–120 per cent was 0.74, a value which is probably insufficient to justify claims of bioequivalence with the reference formulation in respect of extent of availability. In contrast, the posterior probability that the bioavailability of the metabolites isosorbide 2‐ and 5‐nitrate was included within these limits was 0.90 and 0.98, respectively. On the basis of the mononitrate data, these two formulations may be judged bioequivalent in respect of extent of availability despite a formal statistically significant formulation‐related effect in the analysis of variance of the isosorbide 5‐nitrate bioavailability data. Claims of bioequivalence of isosorbide dinitrate sustained‐release formulations may be more economically justified by analysis of the mononitrate plasma concentrations, although concentrations of the formulated

ISSN:0142-2782    

DOI:10.1002/bdd.2510060203

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics of acebutolol and its major metabolite, diacetolol, following a single 400 mg oral dose, were investigated in patients with liver disease. No significant differences were found in any of the parameters measured.

ISSN:0142-2782    

DOI:10.1002/bdd.2510060204

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractDose dependency of the pharmacokinetics of buspirone, a new anxiolytic agent, was tested in 24 healthy volunteers. Each subject received 10, 20, and 40 mg doses according to a randomized, three‐way crossover design with a 7‐day interval between treatments. Buspirone AUC values at 10, 20, and 40 mg doses were in the ratio of 1:1.7:3.5 while Cmaxvalues, had a ratio of 1:1.9:3.7. The dose normalized (10 mg basis) AUC andCmaxvalues,Tmaxvalues, and half‐lives were not significantly different (p>0.05) among the doses. Buspirone half‐life did not change as a function of dose (mg kg−1). It was concluded that buspirone exhibits linear pharmacokinetics following doses in the therapeu

ISSN:0142-2782    

DOI:10.1002/bdd.2510060205

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics of cephalexin and cefadroxil were compared following single 500 mg oral doses to 12 healthy male volunteers. Doses were administered after an overnight fast according to a crossover design. Plasma and urinary levels of both compounds were determined by HPLC procedures. Cephalexin was absorbed rapidly, achieving a mean peak plasma level of 17.5 μg ml−1at 1 h, compared to 16 μg ml−1at 1.8 h for cefadroxil. Elimination half‐lives of cephalexin and cefadroxil were 0.7 and 1.1 h, respectively. The area under the cefadroxil plasma curve was significantly larger than that for cephalexin. However, after allowing for differences in elimination rate constants and assuming equal distribution volumes, plasma data indicated the compounds were equally well absorbed. Only 70 per cent of cefadroxil was recovered in urine compared to 87 per cent of cephalexin during the 12 h following drug administration. The therapeutic significance of the different pharmacokinetic characteristics of cephalexin and cefadroxil, if any, may be a function also of their pharmacologic activity and/or the sensitivity of the target o

ISSN:0142-2782    

DOI:10.1002/bdd.2510060206

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractFour normal volunteers each received two intravenous doses of PA. The mean low dose was 3.30 mg kg−1(infused over 20 minutes) while the mean high dose was 12.5 mg kg−1(infused over 60 minutes). Blood samples were collected for 12 hours and urine was collected for 48 hours after each dose. PA concentrations were determined by both HPLC and fluorescent immunoassay methods. The reported concentrations and pharmacokinetic parameters are from the HPLC data unless otherwise indicated. The mean peak serum PA concentrations resulting from the low and high doses were 3.18 and 9.07 μg ml−1, respectively. Total PA clearance averaged 763 ml min−1and 577 ml min−1while renal clearance averaged 360 ml min−1and 318 ml min−1after the low and high doses, respectively. Concentration‐dependent decreases in nonrenal PA clearance ranged from 31 to 43 percent (p<0.05) in the four subjects. Total clearance decreases ranged from 4.7 to 36 per cent (p<0.05). Differences between doses in renal clearance, elimination rate constant, and volume of distribution were not statistically significant. This study demonstrates that the nonrenal and total clearances of PA are concentration‐dependent in normal subjects at therapeutic plasma PA concentrations and suggests that the total clearance changes are of sufficient magnitude to be cl

ISSN:0142-2782    

DOI:10.1002/bdd.2510060207

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractThe effects of ibuprofen on maternal phenytoin pharmacokinetics and fetal phenytoin acquisition were investigated in 19‐day gestation Sprague—Dawley rats. A 5 mg kg−1bolus injection of14C‐phenytoin was given with and without (control) pretreatment with 12.5 mg kg−1of ibuprofen. Maternal plasma and fetal whole body samples were obtained at various times after the phenytoin bolus and evaluated simultaneously using a three‐compartment maternal‐fetal model. Ibuprofen pretreatment increased the maternal plasma clearance of phenytoin about three‐fold and the overall apparent volume of distribution almost four‐fold. No changes in the volume of the maternal central compartment or terminal first‐order disposition rate constant were observed. Additionally, the maternal‐to‐fetal clearance of phenytoin was not altered in the ibuprofen‐treated rats. No differences in the apparent fetal volume of distribution or areas under the fetal phenytoin concentration‐time curves were observed between the control and ibuprofen‐treated rats. The results of this study were consistent with ibuprofen‐induced alterations in organ and tissue blood perfusion and demonstrated that, while the maternal disposition kinetics of phenytoin were altered by sodium ibuprofen coadministration, the maternal changes did not affect the extent

ISSN:0142-2782    

DOI:10.1002/bdd.2510060208

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractFor single bolus administration, intermittent bolus administrations to steady‐state, a single dose as a zero order input, intermittent zero order inputs to steady‐state, and continuous zero order input to steady‐state, and for both simple Michaelis—Menten elimination and parallel Michaelis—Menten and first order elimination, the appropriate equations are given for the areas, AUC 0–∞ or AUC 0–τ, steady‐state concentrations, and clearances. Some 20 new equations have been derived. For the case of first order input and Michaelis—Menten elimination, no solution is given but the effect of input rate on systemic availability is reported following some numerical integrations.The effect of slow input in reducing systemic bioavailability when Michaelis—Menten elimination kinetics are operative is stressed and the implications of this in the field of sustained‐rele

ISSN:0142-2782    

DOI:10.1002/bdd.2510060209

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractA method for determining the individual pharmacokinetics of endogenous creatinine is derived and applied in 10 post‐renal transplant patients. All patients had rapidly decreasing serum creatinine concentrations (C), but relatively constant creatinine clearance (Clcr) during the study period. Based on the multiple consecutive Clcrand the correspondingC, the elimination rate constant (K), volume of distribution (V), and daily creatinine production rate (R) for each patient were derived. The creatinine ‘normal’ t1/2(corresponding to a Clcrof 120 ml min−1) was also calculated. In the 10 patients studied, the observed Clcrranged from 29.5 to 72.7 ml min−1. The corresponding calculated mean K was 0.076 ± 0.028 h−1; R was 20.0 ± 5.7 mg kg−1day−1, and V was 0.60 ± 0.1 l kg−1. The ‘normal’ t1/2was 4.0 ± 0.93 h. These pharmacokinetic parameters are consistent with those derived from radiotracer studies and other methods reported in the literature. The present study shows that the individual endogenous creatinine pharmacokinetics can be determined by a relatively simple and noninvasive method in certain selected patients if the appropriate serum and urinary creatinine co

ISSN:0142-2782    

DOI:10.1002/bdd.2510060210

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510060211

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY