Introduction Biopharmaceutics history 2

THE KIDNEY 157-162 5
THE KIDNEY
The liver (see Chapter 12) and the kidney are the two major drug-eliminating organs in the body, though drug elimination can also occur almost anywhere in the body. The kidney is the main excretory organ for the removal of metabolic waste products and plays a major role in maintaining the normal fluid volume and electrolyte composition in the body. To maintain salt and water balance, the kidney excretes excess electrolytes, water, and waste products while conserving solutes necessary for proper body function.
In addition, the kidney has two endocrine functions:
(1) secretion of renin, which regulates blood pressure, and (2) secretion of erythropoietin, which stimulates red blood cell production.
Anatomic Considerations
The kidneys are located in the peritoneal cavity. A general view is shown in Fig. 7-3 and a longitudinal view in Fig. 7-4. The outer zone of the kidney is called the cortex, and the inner region is called the medulla. The nephrons are the basic functional units, collectively responsible for the removal of metabolic waste and the maintenance of water and electrolyte balance. Each kidney contains 1-1.5 million nephrons. The glomerulus of each nephron starts in the cortex. Cortical nephrons have short loops of Henle that remain exclusively in the cortex; juxtamedullary nephrons have long loops of Henle that extend into the medulla (Fig. 7-5). The longer loops of Henle allow for a greater ability of the nephron to reabsorb water, thereby producing more concentrated urine.
Blood Supply
The kidneys represent about 0.5% of the total body weight and receive approximately 20%-25% of the cardiac output. The kidney is supplied by blood via the renal artery, which subdivides into the interlobar

RENAL CLEARANCE 163-168 5

DRUG METABOLISM 309-311 2
HEPATIC CLEARANCE 311-312 1
HEPATIC ENZYMES 323-325 2
PHARMACOGENETICS AND DRUG METABOLISM
GENETIC POLYMORPHISMS 358-361 3
CYTOCHROME P-450 ISOZYMES 361-366 5
PHASE II ENZYMES 366-368 2
TRANSPORTERS 367-368 1
PHYSIOLOGIC FACTORS RELATED TO DRUG ABSORPTION 373
NATURE OF CELL MEMBRANES 377-378 1
PASSAGE OF DRUGS ACROSS CELL MEMBRANES 378 -389 1
DRUG INTERACTIONS IN THE GASTROINTESTINAL TRACT 389-390 1
ORAL DRUG ABSORPTION 390-401 11
EFFECT OF DISEASE STATES ON DRUG ABSORPTION 405-407 2
IN VITRO DRUG PRODUCT PERFORMANCE
DRUG PRODUCT PERFORMANCE, IN VITRO: DISSOLUTION AND DRUG RELEASE TESTING 425-429 4
PERFORMANCE OF DRUG PRODUCTS: IN VITRO–IN VIVO CORRELATION 437-441 4
COMPENDIAL METHODS OF DISSOLUTION 429-431 2
ALTERNATIVE METHODS OF DISSOLUTION TESTING 431-434 3
DISSOLUTION PROFILE COMPARISONS 434-436 2
MEETING DISSOLUTION REQUIREMENTS 436-437 1
DRUG PRODUCT PERFORMANCE, IN VIVO: BIOAVAILABILITY AND BIOEQUIVALENCE
DRUG PRODUCT PERFORMANCE 469-471 2
PURPOSE OF BIOAVAILABILITY AND BIOEQUIVALENCE STUDIES 471-472 1
RELATIVE AND ABSOLUTE AVAILABILITY 472-474 2
METHODS FOR ASSESSING BIOAVAILABILITY AND BIOEQUIVALENCE 475-478 3
IN VIVO MEASUREMENT OF ACTIVE MOIETY OR MOIETIES IN BIOLOGICAL FLUIDS 475-478
BIOEQUIVALENCE STUDIES BASED ON PHARMACODYNAMIC ENDPOINTS—IN VIVO PHARMACODYNAMIC (PD) COMPARISON 478-479 1
BIOEQUIVALENCE STUDIES BASED ON CLINICAL ENDPOINTS—CLINICAL ENDPOINT STUDY 479-481 2
IN VITRO STUDIES 481 2