Model predictive control with reinforcement learning for drug delivery in renal anemia management

In patients with renal disease, dosage adjustments are necessary to maintain therapeutic plasma drug concentrations and prevent toxicity or subtherapeutic exposure. Renal impairment alters drug pharmacokinetics, especially in conditions like uremia, where changes such as prolonged elimination half-life and altered apparent volume of distribution can significantly affect drug disposition. These changes require careful modification of the dosing regimen to achieve the desired clinical...

PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure (CHF).

Glomerular filtration rate (GFR) can be estimated from serum creatinine using the modification of diet in renal disease (MDRD) formula or the chronic kidney disease–epidemiology collaboration (CKD–EPI) equation. Both methods are widely used in clinical practice to assess kidney function and guide treatment decisions.The MDRD equation does not require weight or height measurements and is normalized to the body surface area of 1.73 m², considered the average adult surface area. This equation is...

Renal clearance is a crucial parameter in pharmacokinetics that quantifies the rate at which the kidneys excrete a drug. It represents a constant fraction of the central volume of distribution containing the drug that the kidney eliminates per unit of time.
Renal clearance can be calculated using different methods. One approach is to divide the urinary drug excretion rate by the plasma drug concentration. This method directly measures renal clearance, indicating the kidneys' efficiency in...

Modified-release drug delivery systems improve drug efficacy and minimize side effects by controlling the rate and location of drug release. These systems fall into three categories: rate-programmed, stimuli-activated, and site-targeted.Rate-programmed systems release drugs at a predetermined rate, maintaining consistent therapeutic levels and reducing fluctuations that could lead to toxicity or subtherapeutic effects. These systems use polymeric matrices, reservoir-based designs, or osmotic...

The glomerular filtration rate (GFR) is a critical indicator of kidney health, reflecting how well the kidneys filter blood. Changes in GFR can signal potential kidney impairment, necessitating accurate measurement methods to monitor kidney function effectively.Various molecules can serve as markers for GFR measurement, with the ideal marker meeting several specific criteria. It must freely filter at the glomerulus, avoid reabsorption or secretion by the renal tubules, remain unmetabolized, not...