Most drug-drug interactions are what kind of interaction?
How do drugs cross biological barriers?
1) passive diffusion - lipid depends on lipid solubility (depends on lipid partition coefficient P). If aqueous, must pass through or between cells 2) Transport by specific transporters - requires energy usually and drugs can compete with each other
What are the 2 main classes of drug transporters?
1) Uptake - SLC transporters that co-transport sodium 2) Efflux - ABC transporters use ATP
Explain SLCO1B1 (OATP2), liver transporter
-Actively concentrates most statins in hepatocytes and keeps circulating concentrations relatively low - genetic defects are associated with higher incidence of statin-associated myopathy. simvastatin> atorvastatin
What adjustment in simvastatin might you recommend for an individual with a homozygous mutation in the transporter SLCO1B1? Increase, Decrease, or None?