Pharmacokinetics and Pharmacodynamics Relationship

Benchmark – Approved Drug by the FDA

The FDA and similar regulatory agencies approve new drugs and ensure the safety and efficacy of all drugs available for human use (Kayki-Mutlu & Michel, 2021). Comprehending a drug’s safety and efficacy relies significantly on its pharmacokinetics and pharmacodynamics. Pharmacodynamics (PD) pertains to the body’s biological response to drugs, while pharmacokinetics (PK) concerns the passage of drugs through the body. This paper examines the interplay between pharmacokinetics and pharmacodynamics of drugs in absorption, distribution, metabolism, and excretion, focusing on their effects on the human body.

Absorption

Drug absorption is a fundamental principle in pharmacokinetics theory. It refers to transporting the unchanged drug from the administration site to the systemic circulation (Alexander et al., 2021). P-glycoprotein is only one example of a nonspecific drug transporter; additional examples include passive diffusion and carrier-mediated membrane transport methods, including active and assisted diffusion (Kayki-Mutlu & Michel, 2021). Drug absorption can be influenced by various factors, which can be categorized as either drug-specific or patient-specific factors. Also, the proportion of medication absorption varies depending on the route of administration—oral, intramuscular (IM), transdermal, subcutaneous (SQ), and intravenous (IV).

The concentration of a drug in the plasma determines its therapeutic benefit and potential toxicity. The bioavailability of the medicine is an essential factor in keeping the plasma levels of the drug within the acceptable therapeutic range. The bioavailability of a drug is influenced by its absorption rate and extent at the administration site. Factors such as the route of administration directly impact the drug’s absorption and, consequently, its bioavailability (Habet, 2021). Parenteral, rectal, oral, and topical administration are, in order, the modes of administration with the most excellent bioavailability, followed by oral administration and then parenteral administration again. IV drugs have 100% bioavailability as they bypass the absorption process and directly enter the systemic circulation. Tablets, capsules, and solutions are some examples of dosage forms that may be made to be administered by a variety of routes. These dosage forms include the medicine in addition to additional substances. For medications to be absorbed, they must be in solution, regardless of the mode of delivery. Solid dosage forms, such as tablets, should possess the ability to undergo disintegration and disaggregation.

Distribution

Drug distribution refers to the process by which an unchanged drug is transported throughout the bloodstream and various tissues of the body. Distribution is typically uneven due to variations in factors such as blood perfusion, tissue binding (e.g., lipid content), regional pH, and cell membrane permeability (Li et al., 2019). Drugs exhibit varying distribution within different tissue types, including adipose, muscular, and neural tissues, as determined by their molecular structure. The brain and testes possess membrane barriers that distinguish them from other tissues, reducing susceptibility to drug distribution. Drugs can be categorized as lipophilic (soluble in fat) or hydrophilic (soluble in water) based on their solubility in lipids and non-lipids. The higher the proportion of the drug in its un-ionized state, the greater its lipid solubility and propensity for passive diffusion across the membrane. Lipophilic drugs tend to be preferentially distributed to regions with higher concentrations of lipids. Body fat levels can differ based on age, gender, and genetics.

Numerous drugs exhibit binding affinity towards plasma proteins, with albumin and globulins being the primary proteins involved in drug binding. Age, nutritional state, and illness all affect how much of these proteins are present (Zou et al., 2020). Drug effects may be influenced by competition for plasma binding. For instance, it is well-established that aspirin and warfarin vie for the identical binding site on plasma proteins. When both medications are given at the same time, more of the unbound medication will be released, intensifying their effects and perhaps raising the risk of bleeding.

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Metabolism

The liver is the primary organ responsible for drug metabolism. Drug metabolism can render drugs inactive, but specific drug metabolites retain pharmacological activity, sometimes surpassing the original compound (Yu et al., 2020). A prodrug refers to a substance that is inactive or has weak activity but contains an active metabolite. It is mainly designed to enhance the delivery of the active component. Isomerization, hydration, conjugation, reduction, hydrolysis, hydration, oxidation, condensation, or reduction are all methods of drug metabolism; the objective is to facilitate the drug’s excretion. Metabolic enzymes are widely distributed in various tissues, with a higher concentration typically observed in the liver.

There is variability in drug metabolism rates among patients. Changing the route of administration often requires adjusting the dosage. An oral medication, for instance, must travel via the gastrointestinal tract, where it is absorbed in the intestines and metabolized by the liver in the first pass (Jain, 2019). In contrast, IV drugs are assumed to rapidly enter the systemic circulation without being absorbed or metabolized, allowing for accurate dosage determination. The metabolism of numerous drugs follows a biphasic process. Phase I reactions include creating or altering a functional group or breaking chemical bonds through processes such as oxidation, reduction, and hydrolysis. These reactions are considered nonsynthetic. Phase II reactions encompass conjugation with endogenous substances such as glucuronic acid, sulfate, and glycine. These reactions are synthetic.

Excretion

Excretion refers to the elimination of drugs from the body. The kidneys are the primary organs responsible for excretion, although certain drugs may be eliminated through alternative routes such as the lungs, skin, or the gastrointestinal system. Drugs may be eliminated from the body by secretion in the tubules or passive filtration in the glomerulus, which some substances’ reabsorption can hamper. Clearance is a crucial concept in the study of excretion. It is defined as the ratio between the rate at which a drug is eliminated from the body and the concentration of the drug in the plasma. The half-life is the time it takes for blood drug concentrations to fall by half (Deore et al., 2019). Disease or age-related changes in clearance parameters can alter the half-life of medications.

Drug kinetics refers to the graphical representation of a drug’s metabolism and excretion processes, including measuring its half-life. Drug kinetics can be classified into two primary forms: zero-order and first-order. Zero-order kinetics exhibit a consistent metabolic and elimination rate not influenced by the drug’s concentration. According to Yu et al. (2020), the first-order model includes a constant ‘t’ that exhibits a decline in plasma clearance over time. This model represents the primary mechanism of drug elimination for most medications. These kinetic models may calculate pharmaceutical steady states and complete elimination. When the delivery and clearance of a medication are balanced, the plasma concentration remains constant throughout time. When a medicine is supplied by continuous infusion under optimum therapy conditions, this occurs after four to five half-lives of treatment. This is the stage referred to as the steady state of the system. Only adjustments to the dosage, timing of doses, or drug clearance may affect this steady-state concentration.

Conclusion

The comprehension of PK and PD is crucial as it facilitates the comprehension of drug behavior inside the human body and the corresponding physiological responses elicited by medications. Drug developers use insights acquired from PK and PD analysis to enhance the design of clinical trials. Healthcare professionals use the data from PK and PD studies to provide appropriate medical interventions for diverse patient populations. PK/PD analysis and PK/PD modeling are valuable tools for assessing many crucial drug development characteristics about the design of clinical studies for medication approval.

References

Alexander, S. P., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Buneman, O. P., Cidlowski, J. A., Christopoulos, A., Davenport, A. P., Fabbro, D., Spedding, M., Striessnig, J., Davies, J. A., Ahlers‐Dannen, K. E., & Alqinyah, M. (2021). The Concise Guide To Pharmacology 2021/22: Introduction and Other Protein Targets. British Journal of Pharmacology, 178(S1). https://doi.org/10.1111/bph.15537

Deore, A. B., Dhumane, J. R., Wagh, R., & Sonawane, R. (2019). The Stages of Drug Discovery and Development Process. Asian Journal of Pharmaceutical Research and Development, 7(6), 62–67. https://doi.org/10.22270/ajprd.v7i6.616

Habet, S. (2021). Narrow Therapeutic Index drugs: clinical pharmacology perspective. Journal of Pharmacy and Pharmacology, 73(10). https://doi.org/10.1093/jpp/rgab102

Jain, K. K. (2019). An Overview of Drug Delivery Systems. Drug Delivery Systems, pp. 1–54. https://doi.org/10.1007/978-1-4939-9798-5_1

Kayki-Mutlu, G., & Michel, M. C. (2021). A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2020. Naunyn-Schmiedeberg’s Archives of Pharmacology, 394(5), 839–852. https://doi.org/10.1007/s00210-021-02085-3

Li, C., Wang, J., Wang, Y., Gao, H., Wei, G., Huang, Y., Yu, H., Gan, Y., Wang, Y., Mei, L., Chen, H., Hu, H., Zhang, Z., & Jin, Y. (2019). Recent progress in drug delivery. Acta Pharmaceutica Sinica B, 9(6), 1145–1162. https://doi.org/10.1016/j.apsb.2019.08.003

Yu, Y., Diether Rüppel, Weber, W., & Hartmut Derendorf. (2020). PK/PD Approaches. Springer EBooks, 1047–1069. https://doi.org/10.1007/978-3-319-68864-0_26

Zou, H., Banerjee, P., Leung, S. S. Y., & Yan, X. (2020). Application of Pharmacokinetic-Pharmacodynamic Modeling in Drug Delivery: Development and Challenges. Frontiers in Pharmacology, 11. https://doi.org/10.3389/fphar.2020.00997

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Assessment Description

The purpose of this assignment is to analyze the pharmacokinetics and pharmacodynamics relationship in absorption, distribution, metabolism, and excretion to determine how they will react in a human body.

During drug development, pharmacokinetics (PK) and pharmacodynamics (PD) are two key properties used to understand how medications behave in the body and how the body reacts to medications. Use the following objectives to write a 1,000-to-1,250-word paper to help you better understand the PK/PD relationship using the parameters of Absorption, Distribution, Metabolism, and Excretion:

1. Absorption: Compare and contrast the absorption drugs given via the intravascular and extravascular routes. Be sure to include the following that influence drug absorption: local versus systemic effect, dosage form and drug solubility, and bioavailibility as part of your response.
2. Distribution: Briefly explain the process of drug distribution as it occurs throughout the body. Be sure to include the following factors that influence volume of distribution: lipophilicity, molecular weight, ionized state, and protein binding as part of your response.
3. Metabolism: Briefly explain the process of drug metabolism as it occurs for intravascular and extravascular routes of administration. Be sure to include the following that influence drug metabolism: primary site of metabolism, oral versus intravenous drug metabolism, prodrug versus non-prodrug metabolism, and phase I and phase II reactions as part of your response.
4. Excretion: Briefly explain the process of drug excretion as it occurs to remove the drug from the body. Be sure to include the following factors that influence drug excretion: route of excretion (e.g. kidney, liver, gut, lungs, and skin), zero versus first order PK, half-life, and steady state as part of your response.

You are required to cite 5-10 sources to complete this assignment. Sources must be published within the past 5 years and appropriate for the assignment criteria and nursing content.

Prepare this assignment according to the guidelines found in the APA Style Guide, located in the Student Success Center.

This assignment uses a rubric. Review the rubric prior to beginning the assignment to become familiar with the expectations for successful completion.

You are required to submit this assignment to LopesWrite. A link to the LopesWrite technical support articles is located in Class Resources if you need assistance.

American Association of Colleges of Nursing Core Competencies for Professional Nursing Education

This assignment aligns to AACN Core Competencies 1.3

Benchmark Information

This benchmark assignment assesses the following programmatic competencies:

MSN-AGACNP; MSN-FNP

6.3: Assess the pharmacodynamics and the pharmacokinetic impact of pharmacologic therapies in the treatment of diseases and altered states.

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