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Paediatric clinical pharmacology
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
CYP1A2 accounts for approximately 13% of the total cytochrome P450 enzyme expression in the livers of healthy adult humans [26]. Caffeine is a recognised probe to study the activity of CYP1A2 both in vitro and in vivo [27] (Figure 1).
Antipsychotics: pharmacology
Published in Kathy J Aitchison, Karena Meehan, Robin M Murray, First Episode Psychosis, 2021
Kathy J Aitchison, Karena Meehan, Robin M Murray
About 14% of the Caucasian population appears to be deficient in CYP1A2 activity. These individuals may be identified by a functional assay using caffeine (a substrate for CYP1A2). There also seems to be significant interethnic variation, with Japanese subjects showing significantly lower enzyme capacity.153
Metabolism of Terpenoids in Animal Models and Humans
Published in K. Hüsnü Can Başer, Gerhard Buchbauer, Handbook of Essential Oils, 2020
(R)-(+)-Pulegone is present in essential oils of Lamiaceae. Hedeoma pulegioides and Mentha pulegium, both commonly called pennyroyal, contain essential oils that are chiefly pulegone (O'Neil, 2006; Bornscheuer et al., 2014). Pennyroyal herb had been used for inducing menstruation and abortion. In higher doses, however, it may result in central nervous system toxicity, gastritis, hepatic and renal failure, pulmonary toxicity, and death. Commercially available, pennyroyal oils have a pulegone content >80% and are both hepatotoxic and pneumotoxic in mice (Engel, 2003). Though pulegone has been used for flavoring food and oral hygiene products, the pulegone content in foods and beverages is restricted by EU law. At nontoxic concentrations, pulegone is oxidized selectively at the 10-position and further metabolized into menthofuran. In vitro data show that this metabolic pathway is mainly catalyzed by human CYP2E1, and to a lesser extent by CYP1A2 and CYP 2C19 (Khojasteh-Bakht et al., 1999). Alternatively, it may be reduced to menthone, which has been detected in trace levels in urine samples. It might be possible that pulegone is also reduced at the carbonyl group first. Consequently, pulegol is either reduced very efficiently to menthol or rearranged to 3-p-menthen-8-ol (Engel, 2003) (Figure 10.23). In rats, three major pathways have been identified: (a) hydroxylation followed by glucuronidation, (b) reduction to menthone and hydroxylation, and (c) conjugation with glutathione and further metabolism (Chen et al., 2001; Ferguson et al., 2007).
Assessment of Herb-Drug Interaction Potential of Five Common Species of Licorice and Their Phytochemical Constituents
Published in Journal of Dietary Supplements, 2023
Mona H. Haron, Bharathi Avula, Zulfiqar Ali, Amar G. Chittiboyina, Ikhlas A. Khan, Jing Li, Vivian Wang, Charles Wu, Shabana I. Khan
Our results indicate that licorice root extracts could interfere with the metabolism and clearance of pharmaceutical drugs if consumed concomitantly. Extracts that showed > 2-fold (100%) induction in CYP3A4 and CYP1A2 activity could significantly enhance the metabolism of drugs which are substrates of these enzymes, causing faster clearance which could lead to reduced efficacy that may result in treatment failure (13). As millions of patients with HIV/AIDS are put on treatment with the highly active antiretroviral therapy (HAART), drug interactions have become a major concern for healthcare providers. The use of HAART as a combination of three to four drugs creates a potential for antiretroviral (ARV) drug interactions. This is often complicated by adding additional drugs to treat other ailments such as co-morbidities, chronic conditions, and (or) opportunistic infections. It has been observed that most ARV drug interactions involve drugs that interact with CYP enzymes, especially those that are substrates of CYP3A4 (37).
Urinary caffeine and caffeine metabolites, asthma, and lung function in a nationwide study of U.S. adults
Published in Journal of Asthma, 2022
Yueh-Ying Han, Erick Forno, Juan C. Celedón
Caffeine (1,3,7-trimethylxanthine) can be absorbed within 45 min after ingestion. Caffeine is primarily metabolized by CYP1A2 in the liver, where it undergoes successive demethylations and oxidations (9). The half-life of caffeine in adults is typically 2.5 to 5 h (9). The main products of the first steps in caffeine metabolism through demethylations are paraxanthine (1,7-dimethylxanthine), theobromine (3,7-dimethylxanthine), and theophylline (1,3-dimethylxanthine)(9). Caffeine and these primary metabolites are methylxanthines, a purine derived group of pharmacologic agents with bronchodilator properties (10). Caffeine has been used to treat apnea of prematurity (AOP) in infants (11) and shown to slightly improve lung function up to four hours post-ingestion in adults with mild to moderate asthma (12). While theophylline is a mild bronchodilator that has been used to treat asthma (13,14), there is limited and inconclusive evidence of any bronchodilator effects of theobromine (10). Although paraxanthine is the major caffeine metabolite, little is known about paraxanthine and asthma or lung function (9).
Effect of laparoscopic sleeve gastrectomy on drug pharmacokinetics
Published in Expert Review of Clinical Pharmacology, 2021
Kaifeng Chen, Yaqi Lin, Ping Luo, Nan Yang, Guoping Yang, Liyong Zhu, Qi Pei
Caffeine, a marker of liver function, is another widely accepted probe for determining CYP1A2 activity in vivo, given that approximately 90% of caffeine is metabolized by CYP1A2 in the liver [40]. The effect of bariatric surgery on caffeine PK was investigated before surgery as well as at 4 weeks and 6 months after surgery [13]. Patients with obesity showed a similar paraxanthine/caffeine ratio but a lower caffeine and paraxanthine concentration when compared with the normal and overweight groups, which can be explained by the fact that the volume of distribution is considerably increased in individuals with obesity. Following LSG, neither caffeine concentrations nor the paraxanthine/caffeine ratio differed at all postoperative time points compared with the baseline values, indicating that the activity of CYP1A2 is not impaired by bariatric surgery.