The GCC Guidance for Presenting the SPC, PIL and Labeling ...

these are not available, results obtained with other administration routes, otherpharmaceutical forms or doses can be given as alternative.− Basic primary pharmacokinetic parameters, for instance bioavailability, clearance andhalf-life, should be given as mean values with a measure of variability.− Pharmacokinetics items, which could be included in this section when relevant, are givenbelow.a. General introduction, information about whether the medicinal product is a prodrugor whether there are active metabolites, chirality, solubility etc.b. General characteristics of the active substance(s) after administration of themedicinal product formulation to be marketed.• Absorption: complete or incomplete absorption; absolute and/or relativebioavailability; first pass effect; T max ; the influence of food; in case oflocally applied medicinal product the systemic bioavailability.• Distribution: plasma protein binding; volume of distribution; tissue and/orplasma concentrations; pronounced multi-compartment behavior.• Biotransformation: degree of metabolism; which metabolites; activity ofmetabolites; enzymes involved in metabolism; site of metabolism; resultsfrom in vitro interaction studies that indicate whether the new compoundcan induce/inhibit metabolic enzymes.• Elimination: elimination half-lives, the total clearance; inter and/or intrasubjectvariability in total clearance; excretion routes of the unchangedsubstance and the metabolites.• Linearity/non-linearity: linearity/non-linearity of the pharmacokinetics ofthe new compound with respect to dose and/or time; if thepharmacokinetics are nonlinear with respect to dose and/or time, theunderlying reason for the non-linearity should be presented.Page 24 of 52