Optimal sampling theory and population modelling: application to determination of the influence of the microgravity environment on drug distribution and elimination.
Newer mathematical techniques such as optimal sampling theory and NON-linear Mixed Effects Modelling (NONMEM) allow the determination of pharmacokinetics and pharmacodynamics in populations of individuals previously believed to be "too ill" or "too difficult to study." Optimal sampling determines the most information-rich times to sample the system, allowing robust parameter estimates to be determined from the minimal number of samples. NONMEM, by taking the population as the unit of analysis, allows even fragmentary patient data sets to contribute to population parameter estimates. Obviously, the microgravity environment presents extreme logistical difficulties to the performance of traditional pharmacokinetic and pharmacodynamic studies. Examples of the validation of these techniques are presented, which indicates their likely utility in the important task of determining the influence of the microgravity environment on drug distribution and elimination, even accounting for the limitations of support which will be faced in this circumstance.
Drusano
G L
GL
Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore 21201.
D001499:Bayes Theorem; D002442:Ceftazidime / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000493:pharmacokinetics; D003550:Cystic Fibrosis / Q000378:metabolism; D005334:Fever / Q000209:etiology / Q000378:metabolism; D006801:Humans; D008962:Models, Theoretical; D009010:Monte Carlo Method; D009369:Neoplasms / Q000150:complications; D009503:Neutropenia / Q000209:etiology / Q000378:metabolism; D010599:Pharmacokinetics; D010878:Piperacillin / Q000493:pharmacokinetics; D011153:Population; D012494:Sampling Studies; D014893:Weightlessness / Q000009:adverse effects*
D002939:Ciprofloxacin; D002442:Ceftazidime; D010878:Piperacillin