Pharmacokinetics and Pharmacodynamics of Antibiotics in Bone

Chronic osteomyelitis requires prolonged antibiotic treatment, has a high recurrence rate, and can cause irreversible damage. This chapter reviews the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics in bone and presents methods that support optimized evidence-based selection of antibiotic dosage regimens. PK processes include drug absorption from the site of administration into the systemic circulation, distribution from the systemic circulation into tissues, and elimination via metabolism, renal excretion, or both. PD describes the relationship between drug concentrations in plasma or at the target site and the time course of drug effect(s). Once a population PK model has been developed, it can be employed in Monte Carlo simulations to predict the expected concentration time profiles for other than the studied dosage regimens. The probability of achieving a PK/PD target can be predicted and recommendations be made on how to dose an antibiotic to maximize the probability of successful therapeutic outcome.