Kinetic and dynamic data of analgesics and NSAIDs drugs reduce 10X uncertainty factors

Abstract

The risk assessment process must use all available toxicological data and scientific evidence on the adverse effects of chemicals or drugs. The relationship between biological indicators and exposure or tissue burdens is determined by the pharmacokinetic and pharmacodynamic behavior of the chemical. The purpose of the present project was to investigate the use of pharmacokinetic and pharmacodynamic data in reducing the uncertainties in establishing exposure levels for some analgesics and non-steroidal anti-inflammatory drugs (NSAIDs). Five pharmaceuticals were evaluated, namely: naproxen, acetaminophen, aspirin, ibuprofen and ketoprofen. The pharmacokinetic and pharmacodynamic parameters in inter-and intra-species were evaluated. The composite factors for all the examined drugs were far less than 100. The present study indicated that the formation of data basis for different chemicals based on pharmacokinetic and pharmacodynamic behavior is important in setting up exposure levels, rather than the use of default uncertainty factors which are in many cases imprecise.

Intra-Species Extrapolation in Risk Assessment of Different Classes of Antimicrobials

“…They suggested that a factor less than 10 could be used for intrasepecies variability in kinetics. The kinetic and dynamic data of some drugs were compiled and compared between animal and human and between human and sensitive human (Kadry et al 1997;Suh and Abdel-Rahman 1997;Suh et al 1999). They concluded that the composite factor for most of the drugs examined was far less than 100.…”