PubMed · 1975 · 35 citations · 0 references
PharmacyPharmacokineticsPharmacologyPharmacodynamicsPharmacokinetic ModelingPharmacokinetics Of Anticancer AgentsDrug DispositionDrug DistributionIntravenous Anticancer Drug PharmacokineticsPharmacodynamics Of Anticancer AgentsPharmacodynamics Of Anticancer DrugsPharmacokinetics Of Anticancer DrugsBlood FlowDrug Transport In TissuesIntracellular Drug AccumulationIntracellular Drug ConcentrationIntracellular Drug DistributionMembrane Transport DynamicsPharmacokinetic Parameters
A model framework is discussed for a quantitative description of intercompartment drug transport in terms of individual processes involved. It permits joint consideration of blood flow, membrane transport, binding, and enzyme synthesis. Illustrations are drawn from the pharmacokinetics and pharmacodynamics of methotrexate. Special cases include flow and membrane limitation, and a simple expression is derived to estimate the time required for intracellular drug to reach the concentration of high-affinity binding sites. Transport parameters between blood and cerebrospinal fluid are inferred from new clinical data. Lumbar injection provided a reservoir effect which maintained plasma concentration for a prolonged time compared with intravenous injections.