Abduljalil, Khaled’s team published research in Journal of Pharmacokinetics and Pharmacodynamics in 2020-08-31 | CAS: 21829-25-4

Journal of Pharmacokinetics and Pharmacodynamics published new progress about Homo sapiens. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.

Abduljalil, Khaled published the artcilePrediction of maternal pharmacokinetics using physiologically based pharmacokinetic models: assessing the impact of the longitudinal changes in the activity of CYP1A2, CYP2D6 and CYP3A4 enzymes during pregnancy, Application In Synthesis of 21829-25-4, the main research area is metabolizing CYP1A2 CYP2D6 CYP3A4 impact pregnancy; CYP1A2; CYP2D6; CYP3A4; Inter-individual variability; PBPK; Pharmacokinetics; Pregnancy.

Concerns over gestational effects on the disposition of drugs has highlighted the need for a better understanding of drug distribution and elimination during pregnancy. This study aimed at predicting maternal drug kinetics using a physiol. based pharmacokinetic (PBPK) modeling approach focusing on the observed gestational changes in three important Cytochrome P 450 metabolizing enzymes, namely, CYP1A2, CYP2D6 and CYP3A4 at different gestational weeks (GWs). The Pregnancy PBPK model within the Simcyp Simulator V19 was used to predict the pharmacokinetics of sensitive probes to these enzymes; namely caffeine, theophylline, metoprolol, propranolol, paroxetine, midazolam, nifedipine and rilpivirine. PBPK model predictions were compared against clin. data collated from multiple studies for each compound to cover a wide spectrum of gestational ages. Pregnancy PBPK model predictions were within 2-fold error and indicated that CYP1A2 activity is approx. 0.70, 0.44 and 0.30 fold of the non-pregnant level at the end of the first, second and third trimesters, resp. On the other hand, CYP2D6 activity increases by 1.36, 2.16 and 3.10 fold of the non-pregnant level at the end of the first, second and third trimesters, resp. Likewise, CYP3A4 activity increases by 1.25, 1.75 and 2.32 fold of the non-pregnant level at the end of the first, second and third trimesters, resp. The enzymes activity have been qualified throughout pregnancy. Quantified changes in drug dosing are most relevant during the third trimester, especially for drugs that are mainly eliminated by CYP1A2, CYP2D6 and CYP3A4 enzymes. The provided functions describing the continuous changes to the activity of these enzymes during pregnancy are important when modeling long term pharmacokinetic studies where longitudinal modeling or time-varying covariates are used.

Journal of Pharmacokinetics and Pharmacodynamics published new progress about Homo sapiens. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem