Pharmacologic rationale for regional drug delivery

Abstract

Regional drug delivery is an approach designed to improve the selectivity of chemotherapy. When compared with systemic drug administration, regional delivery can potentially increase drug concentrations at tumor sites and/or lower systemic drug exposure. Pharmacokinetic analysis can evaluate or even predict the relative advantage of regional drug delivery. Based on a quantitative analysis of regional drug delivery, some drugs and sites of delivery are more favorable than others. The formulas for the therapeutic advantage of intraarterial, intrathecal, and intraperitoneal delivery have a similar structure. The ratio of total body clearance of a drug to its regional exchange rate is the principal determinant of therapeutic advantage. Thus, the most favorable circumstances for regional delivery are the use of drugs with high total body clearances and/or sites of delivery with low exchange rates. Pharmacodynamic factors must also be considered for the overall assessment of regional delivery.