[Clinical application of bisphosphonate's pharmacokinetic principles]

Abstract

Bisphosphonates are a group of osteotropic substances able to modulate bone metabolism in different ways. They all display similar pharmacokinetic characteristics when administered in proportional dosages and assessed by similar methods. With the exception of olpadronate which is soluble in water, bisphosphonates have poor solubility, and may easily precipitate in the digestive media. In spite of their low digestive absorption (Bioavailability: 0.3-5%), they are effectively administered by oral route. Once in plasma they distribute rapidly, being uptaked by mineralized tissues, plasma proteins or eliminated by renal filtration 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 molecules may be related to the potency of the drug. Within the clinical range of doses, bisphosphonates are not retained in soft tissues. This may explain the lack of extraskeletal collateral effects. Plasma blood levels are scarcely related to the clinical activity. Therefore, dosage may be guided better by biochemical markers of the bone disease than by the standard kinetic variables. On the other hand, dose is independent from age and/or body weight. Only renal impairment may induce additional dose adjustments.