A calculator program for clinical application of the Bayesian method of predicting plasma drug levels.

A pharmacokinetic program that allows individualization of drug dosage regimens through the Bayesian method is described. The program, which is designed for the Hewlett-Packard HP-41 CV calculator, is based upon the one-compartment open model with either instantaneous or zero-order absorption. Individualized estimation of the patient's kinetic parameters (clearance and volume of distribution) is performed by analyzing the plasma levels measured in the patient as well as considering the population data of the drug. After estimating the individual kinetic parameters by the Bayesian method, the program predicts the dosage regimen that will elicit the desired peak and trough plasma levels at steady state. For comparison purposes, the least-squares estimates for clearance and volume of distribution are calculated, and dosage prediction can also be made on the basis of the least-squares estimates. The least-squares estimates can be used to calculate population pharmacokinetic parameters according to the Standard Two-Stage method. Several examples of clinical use of the program are presented. The examples refer to patients with classic hemophilia who were treated with Factor VIII concentrates. In these patients, the Bayesian kinetic parameters of Factor VIII have been estimated through the calculator program. The Bayesian parameter estimates generated by the HP-41 have been compared with those determined by a Bayesian program (ADVISE) designed for microcomputers.

[1]  A W Kelman,et al.  Prediction of response to theophylline in chronic bronchitis. , 1984, British journal of clinical pharmacology.

[2]  A Messori,et al.  A calculator program for least-squares parameter estimation according to the one-compartment kinetic model with zero-order input. , 1984, Computer programs in biomedicine.

[3]  J R Koup,et al.  Multiple-dose non-linear regression analysis program. Aminoglycoside dose prediction. , 1983, Clinical pharmacokinetics.

[4]  R A Robb,et al.  Integrated calculator programs for pharmacokinetic calculations. , 1982, American journal of hospital pharmacy.

[5]  A Messori,et al.  A Calculator Program for Individualizing Factor VIII Dosage , 1984, Drug intelligence & clinical pharmacy.

[6]  J. Raymond,et al.  Use of a pharmacokinetic method for establishing doses of aminophylline to treat acute bronchospasm. , 1981, American journal of hospital pharmacy.

[7]  A W Kelman,et al.  OPT: a package of computer programs for parameter optimisation in clinical pharmacokinetics. , 1982, British journal of clinical pharmacology.

[8]  P K Ng,et al.  Determining aminoglycoside dosage and blood levels using a programmable calculator. , 1980, American journal of hospital pharmacy.

[9]  A Messori,et al.  Pharmacokinetic Predictions Based on a Variable Dosage Frequency in Chronic Treatment , 1983, Drug intelligence & clinical pharmacy.

[10]  Lewis B. Sheiner,et al.  A Microcomputer Drug (Theophylline) Dosing Program Which Assists and Teaches Physicians , 1980 .

[11]  A Messori,et al.  INDIVIDUALIZATION OF FACTOR VIII DOSAGE , 1984, Journal of clinical and hospital pharmacy.

[12]  M V Loertscher,et al.  A Calculator Program for Adjusting Aminoglycoside Regimens That Accounts for Tissue Accumulation in Children and Adolescents , 1982, Drug intelligence & clinical pharmacy.

[13]  L. Sheiner,et al.  Modelling of individual pharmacokinetics for computer-aided drug dosage. , 1972, Computers and biomedical research, an international journal.

[14]  J R Koup,et al.  Single-Point Prediction Methods: A Critical Review , 1982, Drug intelligence & clinical pharmacy.

[15]  Jeffrey R. Koup,et al.  Multiple-Dose Non-Linear Regression Analysis Program , 1983 .

[16]  A Messori,et al.  A New Programmable Calculator Procedure for Individualizing Phenytoin Dosage , 1983, Drug intelligence & clinical pharmacy.

[17]  A W Kelman,et al.  Parameter optimisation in clinical pharmacokinetics. , 1982, Computer programs in biomedicine.

[18]  A Messori,et al.  Pharmacokinetics of factor VIII:C. Appropriateness of the one-compartment model for estimating clearance. , 1983, Il Farmaco; edizione pratica.

[19]  L B Sheiner,et al.  Forecasting individual pharmacokinetics , 1979, Clinical pharmacology and therapeutics.

[20]  D W Bourne,et al.  Use of a programmable hand-held calculator for clinical pharmacokinetics. , 1977, American journal of hospital pharmacy.

[21]  A Messori,et al.  A programmable calculator procedure for parameter estimation according to the two-compartment open model with first order absorption. , 1983, Il Farmaco; edizione pratica.

[22]  A Messori,et al.  Iterative least-squares fitting programs in pharmacokinetics for a programmable handheld calculator. , 1983, American journal of hospital pharmacy.

[23]  J C Mitsuoka,et al.  Individualized estimation of clearance following a loading dose and continuous intravenous infusion using a programmable calculator. , 1983, Computer programs in biomedicine.

[24]  R. Cipolle,et al.  Kinetic model for gentamicin dosing with the use of individual patient parameters , 1977, Clinical pharmacology and therapeutics.

[25]  R. Buice,et al.  The Programmable Hand-Held Calculator , 1979 .

[26]  A Messori,et al.  COMPARATIVE ANALYSIS OF THE PHARMACOKINETIC TECHNIQUES AVAILABLE FOR INDIVIDUALIZING PHENYTOIN DOSAGE , 1983, Journal of clinical and hospital pharmacy.