Veterinary Pharmacology and Toxicology- ICAR JRF/SRF 2024

• Non-Microsomal Metabolic Reactions: Acetylation is an entirely non-microsomal Phase II metabolic pathway.
• Subcellular Compartment: Catalyzed by cytosolic $N$-acetyltransferases (NAT1 and NAT2) residing in the soluble cytoplasmic fraction of hepatocytes and gut mucosal cells (using acetyl-CoA as a cofactor).
• Microsomal Pathways: Glucuronidation is microsomal (membrane-bound UDP-glucuronosyltransferases located on the luminal surface of the smooth endoplasmic reticulum); hepatic cytochrome P450 oxidations are microsomal.

Correct option: (3) Acetylation

• Determinants of Glomerular Filtration: In renal elimination, glomerular filtration of a drug is fundamentally governed by its plasma protein binding.
• Free Drug Fraction: Only the unbound (free) drug fraction in plasma is small enough to pass through the fenestrated glomerular capillary endothelial pores and basement membrane podocyte slit diaphragms ($cutoff \sim 60\text{ kDa}$). Drug molecules bound to large plasma proteins (albumin, $\alpha_1$-acid glycoprotein) cannot be filtered.

Correct option: (2) Plasma protein binding

• Dose-Proportional Steady-State Kinetics:
• At pharmacokinetic steady state under linear (first-order) kinetics, average plasma concentration ($C_{ss}$) is determined by:

• If clearance ($CL$) and bioavailability ($F$) remain constant, the steady-state plasma drug concentration is strictly directly proportional to the dose rate. Therefore, doubling the dose rate will increase steady-state plasma concentration by a factor of 2.0 (Option 2).

Correct option: (2) 20