Title 8. INDIVIDUALIZATION OF DRUG DOSAGE REGIMEN.pdf ✅

PHARMD GURU Page 4  For example, digoxin and other polar drugs (water soluble) show better correlation between unbound volume of distribution (Vu) with lean body mass, which is similar in obese and average persons of the same height and frame, than with total body weight.  In contrast, total body weight may be more relevant for a drug that is highly lipid soluble.  Though renal and hepatic functions are related to body size, obesity may not produce a corresponding increase in hepatic function.  Consequently, the use of total body weight to determine a drug dosage regimen could result in toxic effects if the patient is grossly obese.  Thus, though many drug doses are based on the body weight of the patient (expressed as mg/kg), the influence of obesity or malnourishments is not always considered. 3. GENDER:  Genetic and physiological differences between men and women can influence both PK and PD.  For example, many genes on the Y chromosome, which are expressed only in males, have no counterpart on the X chromosome.  The Y chromosome has genes involved in basic cellular function and some genes on the X chromosome are expressed at higher levels in females.  Gene expression and regulation are likely to be influenced by hormonal differences between males and females.  Genomic imprinting, body size, organ size, body fat, ADME can also affect pharmacological outcome.  Other factors such as gastrointestinal transit time, liver enzyme function and urinary creatinine clearance are influenced by both age and sex.  Across the path of a woman’s life it is necessary to consider the stages of ovarian function to appreciate the potential for drug, sex, and age interactions as they influence rational drug therapy.  Use of oral contraceptives and hormonal changes which occur throughout the menstrual cycle influence pharmacological results.  Necessary considerations during pregnancy are alterations in body composition, cardiac output, pulmonary and renal function as well as changes in immune and gastrointestinal systems.