Obesity related alterations in pharmacokinetics and pharmacodynamics of drugs: emerging clinical implications in obese patients - part I
Bibliographic record
Abstract
Obesity is escalating among children and adults all over the world. This non-communicable disorder contributes heavily to severe morbidity and mortality in humans due to the occurrence of diabetes mellitus, cardiovascular diseases, osteoarthritis, and some cancers. Excess deposition of white adipose tissue in obese patients produces hormone like bioactive substances that produce inflammatory cytokines, atherosclerosis and cardiovascular diseases, to name a few. Obesity can also cause pathophysiologal changes in liver, kidney, and GI tract that can affect drug disposition, resulting in therapeutic failure or toxic drug reactions. Alterations in drug absorption, distribution, metabolism and excretion (ADME), ie. pharmacokinetics (PK) and pharmacodynamics (PD) have been observed in lean and obese patients. A limited number of studies have shown significant differences in the PK parameters such as Vd, CL, t1/2, Tmax, Cmax, and AUC of drugs (e.g., antimicrobials, chemotherapeutics, anesthetics, CNS agents) in obese and lean patients. In view of these observations, clinical responses to medications can markedly differ between non-obese and obese patients, and this phenomenon can lead to improper dosing, often leaving obese patients mistreated for their ailments. Morbidly obese patients are more likely to wake up during surgical interventions done under general anesthesia, especially propofol. It is therefore imparative that the loading and maintinance dose of drugs, especially anesthetics and lipophilic agents, should be adjusted in obese patients. Further, obese men, women and children should be enrolled in clinical trials to determine the safety and efficacy of pharmaceuticals. The focus of this review is to highlight the relationship of obesity-related alterations in drug ADME and to provide an updated overview about the PK and PD changes observed for a wide spectrum of drugs in obese and non-obese patients. Literature-based recommendations for rational therapeutic dose-modifications are also provided in the publication. Keywords: absorption, distribution, metabolism, excretion (ADME), overweight, obesity, pharmacokinetics, pharmacodynamics, drug dose adjustment, obese patients
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".