摘要:

AbstractPharmacokinetic and drug metabolism studies first request that good analytical data are available. The various methods that permit unchanged drugs and their metabolites to be separated, identified and quantitatively assayed are briefly reviewed. The present importance of gas chromatography/mass spectrometry is emphasized, as well as the limits of immunological assays. The sensitivity of the analytical assay has a direct impact on the validity of the pharmacokinetic model which is built up from plasma concentration data. The precision and accuracy of the assay is also critical, and it is not always easily estimated. A new significant parameter is the speed of analysis, and the resulting massive production of analytical data. New drugs coming from biotechnology, and new dosage forms, like targeted drugs, will create new analytical problems in the future. They will probably call for the development of new biological or pharmacological assay procedures, in addition to the physicochemical means of analysis.

ISSN:0142-2782    

DOI:10.1002/bdd.2510070402

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe relative bioavailability of the vasodilator naftidrofuryl from formulations containing its oxalate or citrate salt has been estimated using a specific HPLC assay, and a less specific fluorimetric assay, to measure plasma drug concentrations. The conclusions of the study were the same irrespective of the assay employed. The relative rate, but not the extent, of bioavailability of naftidrofuryl from the citrate salt (peak 1096 ng ml−1at 0·76 h) was marginally greater (p= 0·003) than that from the oxalate salt (peak 922ng ml−1at 0·94 h). The degree of intersubject variability was similar after administration of either salt form. The mean half‐life of naftidrofuryl was 1·8 h and its mean residence time

ISSN:0142-2782    

DOI:10.1002/bdd.2510070403

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe kinetics of ceforanide in plasma and dialysate was studied in 8 patients with terminal renal impairment after undergoing haemodialysis sessions lasting between 4 and 5 h. All patients received a single i.v. dose of 15 mg kg−1of the drug at the start of the session. The dialysers used in this study were Spiraflow capillar 1·3 m2, Travenol plates 1·4 m2, and PAN plates. Blood flow ranged between 200 and 300 ml min−1and dialysate flow between 500–650 ml min−1. Plasma ceforanide levels were measured at the input and output of the dialyser and the antibiotic levels in dialysate were determined coinciding with the withdrawal times of the blood samples. A microbiologic plate diffusion method was used to determine the antibiotic concentrations.The mean values of some pharmacokinetic parameters of ceforanide calculated with a non‐linear regression program from the data obtained from arterial blood were the following: α (h−1) = 4·14 ± 1·32; β (h−1) = 0·26 ± 0·07;t1/2β (h) = 2·82 ± 0·82;Vdss(1) = 10·24 ± 2·14.From the relationships between the antibiotic concentrations at the input and output of the dialyser it was possible to calculate an extraction coeffficient of 0·11 ± 0·06. The dialysis clearance of ceforanide was calculated from the determination of the extraction coefficient and from the measuring of antibiotic in dialysate, though different results were obtained with the two methods. Dialysis clearance calculated from the extraction coefficient showed a mean value of 18·68 ± 12·16 ml min−1, significantly lower (p<0·01) than that established by analysis of the antibiotic in dialysate, which was 41·55 ± 15·83 ml min−. These differences may be attributed to problems related to the determination of blood flow and to the ultrafiltration capacity of the dialysis membranes. A linear relationship was established between the percentage error in the observed and predicted extraction coefficients and the ultrafiltration rate. The results obtained suggest that the simultaneous measurement of the antibiotic in plasma and dialyate is the most suitable method for predicting the dialysis clearance of the drug. The amount of antibiotic extracted over a 4‐hour dialysis session proved to be equal to 5

ISSN:0142-2782    

DOI:10.1002/bdd.2510070404

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractAn evaluation of the literature indicated that certain aspects of the disposition kinetics of iothalamate, important to the accurate determination of glomerular filtration rate in dogs and humans, remain to be resolved. The simultaneous clearances of iothalamate and inulin in 5 dogs were determined at three steady‐state iothalamate plasma levels (2, 10, and 40μg ml−1) following various rates of intravenous infusion. The iothalamate clearances, both renal and non‐renal, were concentration‐independent. The overall mean non‐renal clearance was 18 per cent (ranging from 9 to 25 per cent) of its plasma clearance. The mean iothalamate/inulin renal clearance ratio was about 0·84 with individual values ranging from 0·72 to 0·95. The significant (4–26 per cent) plasma protein binding of iothalamate in these dogs was the main reason for the lower‐than‐unity clearance ratios obtained. The literature indicates the existence of up to 25 per cent of non‐renal elimination in humans with normal renal function; this is comparable to the present results obtained with dogs but contrary to the assumption, sometimes reported in the literature that non‐renal elimination is essentially absent in humans. Binding of iothalamate to plasma proteins from humans was not found in the present study. The above results suggest that for accurate glomerular filtration rate determination in humans and dogs, especially for those with renal impairment, renal clearance rather than plasma clearance should be used, and in the case of dogs it should also be corrected for plasma protein binding. Iothalamate in plasma and urine was analysed by a simple, micro high‐performance liquid chromatographic

ISSN:0142-2782    

DOI:10.1002/bdd.2510070405

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractEncapsulation in liposomes of the antitumoral drug 2‐methyl 9‐hydroxyellipticinium and the consequences of its cytoxicityin vitroon L1210 leukemia cells and on its antitumoral activityin vivoon leukemic mice inoculated with L1210 cells are described. Provided the drugs is dissolved in the buffer below its critical micelle concentration (10−4M), it can be encapsulated in lipid vesicles with a very good yield in the form of a very stable combination with the lipids. Thein vitroexperiments show that 2‐CH39‐OH‐ellipticinium is less cytotoxic against L1210 cells when entrapped than when free in solution. Thein vivoexperiments on tumor‐bearing mice show that encapsulation of the drug reduces its toxicity. Encapsulation maintains the antitumoral activity of the drug or increases it if the leukemia is delayed (104cells injected per mouse instead of 105cel

ISSN:0142-2782    

DOI:10.1002/bdd.2510070406

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics and pharmacodynamics of trimazosin are described following both intravenous and oral administration to 6 normotensive, male volunteers. The IV and oral drug and metabolite (1‐hydroxytrimazosin) concentration data are fitted simultaneously to the same pharmacokinetic model. The pharmacodynamic response, change in systolic blood pressure following 5 min in the erect posture, is described using several possible models. The most efficient is one which attributes the response to both the parent drug and its principal metabolite. The response following oral administration is also consistent with this model.It appears that the reduction in blood pressure following administration of trimazosin at steady state may be governed by the concentration of metabolit

ISSN:0142-2782    

DOI:10.1002/bdd.2510070407

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractCrotethamide and cropropamide, both components of the respiratory stimulant prethcamide, are metabolized in humans by demethylation of the [(dimethylamino)‐carbonyl]‐propyl moiety. The resulting metabolites are characterized by gas chromatography–mass spectrometry of urinary extracts. The use of HCl to prevent losses by volatilization during the evaporation step, combined with methanol as solvent, complicates gas liquid chromatographic analysis of prethcamide. The resulting artifacts are ident

ISSN:0142-2782    

DOI:10.1002/bdd.2510070408

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510070409

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510070410

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

ISSN:0142-2782    

DOI:10.1002/bdd.2510070401

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY