Current Drug Metabolism - Volume 17, Issue 7, 2016

Background: The interest in administering drugs by intranasal route is currently increasing, particularly because it has shown to ensure drug therapeutic action by a rapid systemic absorption through the respiratory mucosa and/or a direct delivery of some molecules into the brain through the olfactory mucosa. Nevertheless, although intranasal administration avoids the first-pass hepatic biotransformation, several enzymes Read More

Background: Certain therapeutic drugs used in medical practice may trigger mitochondrial toxicity leading to a wide range of clinical symptoms including deafness, neuropathy, myopathy, hyperlactatemia, lactic acidosis, pancreatitis and lipodystrophy, among others, which could even compromise the life of the patient. Objectives: The aim of this work is to review the potential mitochondrial toxicity derived from drugs u Read More

Chronic kidney disease (CKD) modulates the nonrenal clearance of drugs by altering their metabolism and/or transport. While the effects of CKD on pathways of oxidative and conjugative metabolism in the liver are generally understood, the impact of CKD on hepatic reduction is not. Reduction is a critically important pathway for the metabolism of several drugs and endogenous compounds. Multiple clinical pharmacokinetic studie Read More

Background: In drug metabolism reactions, it has become increasingly important to measure Michaelis constants (Km), which are used for a variety of purposes, including identification of enzymes involved in drug metabolism, prediction of drug-drug interactions, etc. Cytochrome P450s (CYPs) comprise a super family of major human enzymes responsible for drug metabolism. Hence, computational prediction of Km in CYP-medi Read More

Background: Angiotensin receptor blockers (ARBs) are the most recent class of agents for the treatment of hypertension. However, ARBs may cause a low incidence of headache, upper respiratory infection, back pain, muscle cramps, fatigue, dizziness, and many other side effects. In some cases, such toxicity is associated with pharmacokinetic alterations. Methods: The cytochrome P450 (CYP) enzyme system plays an impor Read More

Background: Proton pump inhibitors (PPIs) are a group of gastric acid suppressing drugs, they work by irreversibly blocking the H+/K+ ATPase. The structure of PPIs is similar. They all have a similar core with a sulphur atom chiral center combined with different substituent groups. In relation to the sulphur atom chiral center, the pharmacodynamics, pharmacokinetics are diverse between the racemates and their stereoisomers. Read More

Background: During the last few years there has been a growing interest in research focused on the metabolism of steroid hormones despite that the study of metabolic hormone pathways is still a difficult and demanding task because of low steroid concentrations and a complexity of the analysed matrices. Thus, there has been an increasing interest in the development of new, more selective and sensitive methods for mo Read More

Background: It was reported that phenytoin can prevent early post traumatic seizures. The present study aims to establish a population pharmacokinetic (PPK) model of oral phenytoin in patients with intracranial tumor during the early periods, the first week, of post-craniotomy to optimize phenytoin dosage regimen. Methods: Sixty-two patients with intracranial tumor were genotyped for CYP2C9 and CYP2C19 by re Read More