Insufficient ketoconazole concentrations in preterm infants with fungal infections

Anker, Johannes N. van den; Lingen, Richard A. van; Koster, M.; Heykants, J.; Sauer, Pieter

doi:10.1007/bf01955070

Cited by 8 publications

(5 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Perhaps the fact that preterm infants receive virtually continuous oral feeds containing acid‐buffering milk might result in higher pH values than those seen in more mature infants. That might explain the reduced absorption of weak acids such as phenytoin because of increased ionization as well as reduced absorption of weak bases such as ketoconazole because of decreased solubility …”

Section: Absorption Of Drugsmentioning

confidence: 99%

“…That might explain the reduced absorption of weak acids such as phenytoin because of increased ionization 14 as well as reduced absorption of weak bases such as ketoconazole because of decreased solubility. 15 Gastric emptying and intestinal motility are the primary determinants of the rate and extent of intestinal drug absorption, and until very recently it was assumed that gastric emptying was much slower below the age of 6-8 months because of the immaturity of the neuroregulation of gastric motility. 16 This prolonged gastric emptying should result in a decreased absorption rate and a delay of absorption of drugs that are dependent on the rate and extent of gastric emptying.…”

Section: Absorption Of Drugsmentioning

confidence: 99%

See 1 more Smart Citation

Developmental Changes in Pharmacokinetics and Pharmacodynamics

Anker

Reed

Allegaert

et al. 2018

The Journal of Clinical Pharma

229

171

View full text Add to dashboard Cite

Effective drug therapy to optimally influence disease requires an understanding of a drug's pharmacokinetic, pharmacodynamic, and pharmacogenomic interrelationships. In pediatrics, age is a continuum that can and does add variability in drug disposition and effect. This article addresses the many important factors that influence drug disposition and effect relative to age. What is known about the influence of maturation on the processes of drug absorption, distribution, metabolism, excretion, and drug receptor dynamics are outlined. Our state of understanding of many of these factors remains in flux, however, and only with additional study will we be able to better anticipate and model drug‐response relationships across the age continuum. Being able to continuously improve our care of the ill pediatric patient while simultaneously being able to accurately determine the utility of new drugs and chemical entities in this population requires our enhanced understanding of these disposition characteristics.

show abstract

Section: Absorption Of Drugsmentioning

confidence: 99%

Section: Absorption Of Drugsmentioning

confidence: 99%

Developmental Changes in Pharmacokinetics and Pharmacodynamics

Anker

Reed

Allegaert

et al. 2018

The Journal of Clinical Pharma

229

171

View full text Add to dashboard Cite

show abstract

“…These variations in pH may influence ionizable drugs, affecting absorption by changes in the relative amount of unionized drug available [30]. Lower levels of gastric pH might be involved in the enhanced bioavailability of weak bases by increasing their solubility [31,32]. Conversely, weak acids in a more acid environment are less ionized, so dissolution is decreased and absorption is thus reduced [29,32].…”

Section: Figurementioning

confidence: 99%

Biopharmaceutical optimization in neglected diseases for paediatric patients by applying the provisional paediatric biopharmaceutical classification system

Sanchez

González‐Álvarez

Cerda-Revert

et al. 2018

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…F a was changed from 0.9 to 0.78 to match the Cmax in individuals aged 12 to 17 years. Based on the literature, [18][19][20] it is expected that gut motility and absorption in children is slower and reduced compared with adults. AUC overprediction indicated that the current mechanistic PBPK model needs improvement for use in the specific context of pediatric PK predictions.…”

Section: Pbpk Model Exposure Predictions In Ddis With Rifampin and Mementioning

confidence: 99%

Model‐Informed Pediatric Dose Selection for Dapagliflozin by Incorporating Developmental Changes

Reddy

Parkinson

et al. 2021

CPT Pharmacom & Syst Pharma

View full text Add to dashboard Cite

This analysis reports a quantitative modeling and simulation approach for oral dapagliflozin, a primarily uridine diphosphate-glucuronosyltransferase (UGT)-metabolized human sodium-glucose cotransporter 2 selective inhibitor. A mechanistic dapagliflozin physiologically based pharmacokinetic (PBPK) model was developed using in vitro metabolism and clinical pharmacokinetic (PK) data and verified for context of use (e.g., exposure predictions in pediatric subjects aged 1 month to 18 years). Dapagliflozin exposure is challenging to predict in pediatric populations owing to differences in UGT1A9 ontogeny maturation and paucity of clinical PK data in younger age groups. Based on the exposure-response relationship of dapagliflozin, twofold acceptance criteria were applied between model-predicted and observed drug exposures and PK parameters (area under the curve and maximum drug concentration) in various scenarios, including monotherapy in healthy adults (single/multiple dose), monotherapy in hepatically or renally impaired patients, and drug-drug interactions with UGT1A9 modulators, such as mefenamic acid and rifampin. The PBPK model captured the observed exposure within twofold of the observed monotherapy data in adults and adolescents and in special population. As a guide to determining dosing regimens in pediatric studies, the verified PBPK model, along with UGT enzyme ontogeny maturation understanding, was used for predictions of dapagliflozin monotherapy exposures in pediatric subjects aged 1 month to 18 years that best matched exposure in adult patients with a 10-mg single dose of dapagliflozin. Dapagliflozin (Farxiga, AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA) is an oral medication developed to treat type 2 diabetes mellitus (T2DM) through selective and reversible inhibition of human sodium-glucose cotransporter 2, the major transporter for renal glucose reabsorption. 1 Dapagliflozin reduces plasma glucose by inhibiting renal glucose reabsorption in the renal proximal tubule to promote glucose urinary excretion. Dapagliflozin 10-mg oral tablet is approved in 89 countries for the treatment of T2DM as monotherapy or in combination with other antidiabetic drugs in adults. 2 Recent evidence shows that dapagliflozin reduces the incidence of cardiovascular events, such as heart failure (HF), with clinically meaningful significance. A large, randomized,

show abstract

Insufficient ketoconazole concentrations in preterm infants with fungal infections

Cited by 8 publications

References 5 publications

Developmental Changes in Pharmacokinetics and Pharmacodynamics

Developmental Changes in Pharmacokinetics and Pharmacodynamics

Biopharmaceutical optimization in neglected diseases for paediatric patients by applying the provisional paediatric biopharmaceutical classification system

Model‐Informed Pediatric Dose Selection for Dapagliflozin by Incorporating Developmental Changes

Contact Info

Product

Resources

About