摘要:

AbstractThe pharmacokinetics of Cefoxitin were studied in rabbits with normal renal function and with varying degrees of renal impairment induced experimentally by uranyl nitrate. All animals received a single intramuscular (i.m.) dose of 40 mg kg−1of the antibiotic. The concentrations of Cefoxitin were determined in plasma, urine, and bile by a microbiologic plate diffusion method. The antibiotic follows a two‐compartment open kinetic model. In rabbits with renal impairment there is a decrease in α, β K12, K12, Kaand an increase in Vdand the (AUC) 0∞with respect to the values obtained for rabbits with normal renal function. Linear relationships are established between log β and logK13and the serum creatinine. Biliary excretion of Cefoxitin is increased in states of renal impairment. A linear relationship is established between the percentage of the dose excreted in bile and the serum

ISSN:0142-2782    

DOI:10.1002/bdd.2510020302

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractIt has previously been documented that substantially different aqueous humour drug levels are observed in rabbits of different ages when the same dose of pilocarpine is instilled into the eye. Also, it has been shown that the aqueous humour volume ratio for rabbits of different ages can be used to predict aqueous humour levels of pilocarpine attained after topical dosing. In the present study, concentrations of pilocarpine in the cornea, aqueous humour, iris‐ciliary body, lens, and vitreous humour were determined in both 20‐day old and 60‐day old rabbits following the topical administration of identical doses of drug. For tissues other than the aqueous humour and iris‐ciliary body, consideration of only tissue size differences between rabbits of different ages will not suffice to explain the observed differences in pilocarpine concentration. Any attempt to develop rational age‐related dosage modifications for ophthalmic drugs must include a consideration of functional and developmental differences as well as siz

ISSN:0142-2782    

DOI:10.1002/bdd.2510020303

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractWhen drug‐protein binding data are evaluated thermodynamically standard free energy (ΔG°), standard enthalpy (ΔH°) and standard entropy (ΔS°) are usually estimated from association constants(Ka) derived from binding data obtained at only two temperatures. Estimation of ΔH° involves the assumption of its constancy in the temperature range studied and linearity of a van't Hoff plot of InKaversus 1/T.Sometimes the assumption of such linearity is invalid for theoretical reasons and data obtained at only two temperatures contain no information concerning linearity of this plot. We present data for the binding of both tolmetin and salicylic acid to human serum albumin as a function of temperature which make doubtful the validity of using association constants of these drugs to derive thermodynamic constants other than

ISSN:0142-2782    

DOI:10.1002/bdd.2510020304

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics of noreximide in the rat after i.v., p.o., and i.p. administration was studied. The biologic half‐life of approximately 8 h was found almost the same for all three routes. Upon p.o. administration the fraction of drug absorbed is 85 per cent, and the peak concentration in the blood is reached within approximately 4.5 h. Additional pharmaco‐kinetic parameters are lis

ISSN:0142-2782    

DOI:10.1002/bdd.2510020305

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractWhen isosorbide 5‐mononitrate was intravenously infused at a rate of 4 mg h−1for 2.5 h to five human subjects, its concentrations in plasma increased slowly to 185 ng ml−1± 5 per cent C.V. at 2.5 h and a steady‐state plasma level was not reached during the infusion. When the infusion was discontinued, plasma drug concentrations declined with an elimination half‐life of 4.2 h ± 6 per cent C.V. The systemic clearance after the infusion doses was 132 ml min−1± 18 per cent C.V. and the volume of distribution was 48.4 1 ± 16 per cent C. V. After equal oral doses of 10 mg, the peak plasma isosorbide 5‐mononitrate concentration of 191 ng ml−1±16 per cent C.V. was reached at 1.1 h ± 30 per cent C.V., and plasma levels declined with a terminal half‐life of 4.9 h. The complete systemic availability of isosorbide 5‐mononitrate indicated that pre‐systemic elimination after the oral doses was negligible. A one‐compartment open model appeared adequate to describe the plasma level data after intravenous infusion and oral doses. After single oral doses of 10 mg isosorbide dinitrate, the peak plasma concentration of the 5‐mononitrate metabolite of 72 ng ml−1± 27 per cent C. V. occurred at l.7h.41 per cent C.V. Approximately 50 per cent (range 22–68 per cent) of the oral dose of isosorbide dinitrate circulated in plasma as the 5‐mononitrate metabolite. The pharmacokinetics of isosorbide mononitrates are markedly different to those of the parent dinitrate and these differences follow from the greater systemic availability and volu

ISSN:0142-2782    

DOI:10.1002/bdd.2510020306

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractTwo betamethasone tablet formulations, and a betamethasone phosphate solution were compared in a plasma level study. The tablet formulations (A and B) and a solution of betamethasone phosphate (C) were administered in single 2 mg doses to nine volunteers according to a three times repeated Latin square design. Plasma samples were obtained over 27 h following each dose and plasma was analysed for betamethasone by radioimmunoassay.Pharmacokinetic evaluation of the data, obtained according to the one‐compartment open model, indicated that there were no significant differences between the extent of absorption, and the first‐order elimination rate constants. As would be expected, the solution (C) gave a faster absorption rate than tablets A an

ISSN:0142-2782    

DOI:10.1002/bdd.2510020307

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractThe plasma concentrations and bioavailability of sustained‐release isosorbide denigrate and standard‐release pindolol have been compared after administration of these drugs in combination and alone.Bioavailability parameters of isosorbide dinitrate and pindolol obtained after administration of the drugs in combination were not significantly different (P>0.05) to those obtained after administration of either drug alone.Two peaks of mean concentrations of isosorbide dinitrate occurred in plasma after administration of 30 mg of this drug in combination with 7.5 mg pindolol (4.4 ng ml−1at 1 h and 4.5ng ml−1at 5h), or alone (5.9ngml−1at 2h and 5.7ng ml−1at 5h). In each case, plasma concentrations of isosorbide dinitrate were maintained during at least 8 h, whereas the drug was not detected in plasma at 2.5 h after administration of a standardrelease formulation.The peaks of mean concentrations of pindolol were 39.7ng ml−1at l.5h after administration of 7.5 mg drug in combination with isosorbide dinitrate and 38.0 ng ml−1at 1 h after administration of the drug alone. Concentrations of pindolol in plasma declined with a h

ISSN:0142-2782    

DOI:10.1002/bdd.2510020308

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractIn the past several years bone imaging has become a routine diagnostic tool for the nuclear medicine clinician. However, increased information may be derived by determinating the radio‐pharmacokinetic parameters associated with blood, urine, and bone. In an adult male population of normals(N= 5–6) blood clearance, urinary excretion, and skeletal uptake of99mTc‐Diphosphonate were determined as a function of time after intravenous (i.v.) administration. The quantitative imaging studies (lower lumbar region) were performed up to 1 h post administration with a scintillation camera interfaced to a computer. Blood levels exhibited a triexponential clearance pattern and urinary excretion of the radiopharmaceutical was essentially complete by 4 h. The computer‐generated images showed an initial early uptake in bone, kidneys, and soft tissue. Thereafter, a parallel fall‐off in activity was observed in kidneys and soft tissue, with a concomitant increas

ISSN:0142-2782    

DOI:10.1002/bdd.2510020309

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

摘要:

AbstractPrevious work has shown that after a single oral dose, plasma propranolol concentrations in patients with active inflammatory disease are significantly higher than those in healthy subjects.After oral administration of propranolol (2 mg) to arthritic rats, the area under the mean drug concentration‐time curve in plasma was approximately 10 times greater than that in control animals. After intravenous administration (0.25 mg) the area in arthritic rats was approximately doubled compared with that in controls.The mechanisms causing these changes are not known, but it is probable that increased drug binding to an acute phase reactant in plasma, together with decreased first‐pass hepatic clearance in arthritic rats after oral dosing, are invol

ISSN:0142-2782    

DOI:10.1002/bdd.2510020310

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510020311

出版商:John Wiley&Sons, Ltd.    

年代:1981

数据来源: WILEY