Explain How Changes in PK and PD Might Affect Patient HM’s Recommended Drug Therapy.
Bio pharmaceutics and Drug Disposition
Bio pharmaceutics and Drug Disposition
The Effect of Gender on the Pharmacokinetics (PK) and Pharmacodynamics (PD) of Drug Treatment in Diabetes, Hypertension, Hyperlipidemia, and Ischemic Heart Disease
Gender is one of the factors that have been known to influence differently the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs in men and women. In response to drug treatment as in the case of patient HM, men and women show differences in absorption, distribution, metabolism, excretion (ADME), and response to different drugs (Soldin & Mattison, 2009). For instance, there will be a difference in the oral bioavailability of the drugs patient HM has been put on as a result of gender differences in metabolic enzymes. This difference in absorption and distribution has been observed experimentally even after normalisation for weight. The reason therefore is that men and women also differ in protein binding capacity as a result of intrinsic hormonal differences (Beierle at al., 1999). Bio pharmaceutics and Drug Disposition
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Most importantly, however, there is a significant gender difference in both gut and hepatic levels of the cytochrome (CYP) P450 isoenzyme CYP3A4. This significantly affects the bioavailability of some medications because women have been shown to have 1.4 times the level of this isoenzyme that men have (Beierle et al., 1999; Harris et al., 1995). The importance of this is in the fact that CYP3A4 isoenzyme is involved in the phase I metabolism of over 50% of drugs that are used to treat illnesses in humans. What this means is that since women have higher levels of the isoenzyme, they metabolise many drugs more rapidly than men (Soldin & Mattison, 2009). This may lead to lower bioavailability of these medications.
Another way in which gender might affect the PK and PD processes of the drugs given to patient HM is in the distribution of muscular and adipose tissue. These body compositions are different in men and women. Women have a higher body fat compared to lean mass. This is not the case for men. Since some drugs depend on the proportion of body fat for distribution, it follows that they will be better distributed in women than men, with better bioavailability. Absorption of some drugs is thus affected by the distribution of lean muscular tissue and fatty tissue, with women being lighter but with more body fat (Beierle et al., 1999).
How Changes in PK and PD Might Affect Patient HM’s Recommended Drug Therapy
Because of differences in drug metabolism in both phase I and phase II, some of the drugs will be affected in terms of pharmacokinetics. For instance, in phase II of drug metabolism the conjugation in the liver of salicylic acid in aspirin (acetyl salicylic acid or ASA) is lower in females than in males. This gives rise to a higher concentration in the plasma of aspirin after oral administration in women. Since patient HM is on aspirin, this pharmacokinetic parameter will be impacted accordingly depending on the patient’s gender (Beierle et al., 1999). Zhu and Shin (2005) also demonstrated that there is both slow absorption and reduced metabolism of warfarin in female rats. Bio pharmaceutics and Drug Disposition
How to Improve Patient HM’s Drug Therapy Plan
The dose of ASA may have to be reduced if the patient is female, from the PK process changes seen above. This will reduce the risk of toxicity from an overconcentration of the drug. The dose of warfarin may also be reduced for the same reason, since it is metabolised slowly in females.
References
Beierle, I., Meibohm, B. & Derendorf, H. (1999). Gender differences in pharmacokinetics and pharmacodynamics. International Journal of Clinical Pharmacology and Therapeutics, 37(11), 529-547.
Harris, R.Z., Benet, L.Z. & Schwartz, J.B. (1995). Gender effects in pharmacokinetics and pharmacodynamics. Drugs, 50(2), 222-239
Soldin, O.P. & Mattison, D.R. (2009). Sex differences in pharmacokinetics and pharmacodynamics. Clinical Pharmacokinetics, 48(3), 143-157. Doi: 10.2165/00003088-200948030-00001
Zhu, X. & Shin, W.G. (2005). Gender differences in pharmacokinetics of oral warfarin in rats. Biopharmaceutics and Drug Disposition, 26, 147-150. DOI: 10.1002/bdd.442 Bio pharmaceutics and Drug Disposition