CLINICAL-EVALUATION OF BISPHOSPHONATES PHARMACOKINETIC PRINCIPLES

Bisphosphonates are a group of osteotropic substances able to modulate bone metabolism in different ways. They all display similar pharmacok inetic characteristics when administered in proportional dosages and a ssessed by similar methods. With the exception of olpadronate which is soluble in water, bisphosphonates have poor solubility, and may easil y precipitate in the digestive media. In spite of their low digestive absorption (Bioavailability: 0.3-5%), they are effectively administere d by oral route. Once in plasma they distribute rapidly, being uptaked by mineralized tissues, plasma proteins or eliminated by renal filtra tion in few minutes. The fraction retained in bones may be stored for long periods (from months up to 10 years depending on the compound) in an apparent inactive compartment. The risks of newly released molecul es may be related to the potency of the drug. Within the clinical rang e of doses, bisphosphonates are not retained in soft tissues. This may explain the lack of extraskeletal collateral effects. Plasma blood le vels are scarcely related to the clinical activity. Therefore, dosage may be guided better by biochemical markers of the bone disease than b y the standard kinetic variables. On the other hand, dose is independe nt from age and/or body weight. Only renal impairment may induce addit ional dose adjustments.