First pass effect When a drug is administered orally,the drug is absorbed by the mesenteric veins.These veins drain into the portal vein which flows into the hepatic sinusoids.For some drugs,a substantial portion of the dose is removed and metabolized by the hepatocytes in its first pass through the liver before the drug enters the systemic circulation.Also evidence that significant first pass metabolism can occur in Gl epithelial cells. The rectal route of administration demonstrates a minimal first pass effect. If equieffective doses are administered,the following rank order describes the speed of effect: IV>IM>SC>Oral and the following rank order describes the duration of the effect: Oral>SC>IM>IV Absorption:drug transport Movement of Drugs across membranes: Active Transport:i)energy dependent;ii)saturable;ii) against an electrochemical gradient;iv)selective carrier- mediated Facilitated Diffusion:i)requires NO energy;ii)saturable;iii) NEVER against an electrochemical gradient;iv)selective carrier-mediated. Pinocytosis:Drugs of large molecular weight(MW>900)may enter cells by pinocytosis or phagocytosis. Passive Diffusion:This is the MOST COMMON mechanism for drug transport.Lipid-soluble drugs permeate across the cell membrane by passive diffusion between the lipid molecules of the cell membrane.First pass effect • When a drug is administered orally, the drug is absorbed by the mesenteric veins. These veins drain into the portal vein which flows into the hepatic sinusoids. For some drugs, a substantial portion of the dose is removed and metabolized by the hepatocytes in its first pass through the liver before the drug enters the systemic circulation. Also evidence that significant first pass metabolism can occur in GI epithelial cells. • The rectal route of administration demonstrates a minimal first pass effect. • If equieffective doses are administered, the following rank order describes the speed of effect: IV > IM > SC > Oral and the following rank order describes the duration of the effect: Oral > SC > IM > IV Absorption: drug transport • Movement of Drugs across membranes: • Active Transport: i) energy dependent; ii) saturable; iii) against an electrochemical gradient; iv) selective carrier‐ mediated. • Facilitated Diffusion: i) requires NO energy; ii)saturable; iii) NEVER against an electrochemical gradient; iv) selective carrier‐mediated. • Pinocytosis: Drugs of large molecular weight (MW > 900) may enter cells by pinocytosis or phagocytosis. • Passive Diffusion: This is the MOST COMMON mechanism for drug transport. Lipid‐soluble drugs permeate across the cell membrane by passive diffusion between the lipid molecules of the cell membrane