Impact of SLC22A1 and CYP3A5 genotypes on imatinib response in chronic myeloid leukemia: A systematic review and meta-analysis

Cargnin, Sarah; Ravegnini, Gloria; Soverini, Simona; Angelini, Sabrina; Terrazzino, Salvatore

doi:10.1016/j.phrs.2018.02.005

Cited by 21 publications

(14 citation statements)

References 41 publications

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“…In the one study on Chinese patients with epilepsy, a statistically significant association between SLC22A1 rs628031 polymorphism and normalized LTG concentration has been observed (Shen et al, 2016). However, for other drugs transported by OCT1, there are contrasting reports regarding the roles of rs628031 polymorphisms in the treatment response or drug-related adverse effects (Tarasova et al, 2012; Koren-Michowitz et al, 2014; Cargnin et al, 2018). The studied single nucleotide polymorphisms (SNPs) for SLC22A1 are also limited in Chinese people, and more research is needed to obtain a solid basis to design personalized therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

Effects of Comedication and Genetic Factors on the Population Pharmacokinetics of Lamotrigine: A Prospective Analysis in Chinese Patients With Epilepsy

et al. 2019

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Lamotrigine (LTG) is a second-generation anti-epileptic drug widely used for focal and generalized seizures in adults and children, and as a first-line medication in pregnant women and women of childbearing age. However, LTG pharmacokinetics shows high inter-individual variability, thus potentially leading to therapeutic failure or side effects in patients. This prospective study aimed to establish a population pharmacokinetics model for LTG in Chinese patients with epilepsy and to investigate the effects of genetic variants in uridine diphosphate glucuronosyltransferase (UGT) 1A4, UGT2B7, MDR1, ABCG2, ABCC2, and SLC22A1, as well as non-genetic factors, on LTG pharmacokinetics. The study population consisted of 89 patients with epilepsy, with 419 concentrations of LTG. A nonlinear mixed effects model was implemented in NONMEM software. A one-compartment model with first-order input and first-order elimination was found to adequately characterize LTG concentration. The population estimates of the apparent volume of distribution (V/F) and apparent clearance (CL/F) were 12.7 L and 1.12 L/h, respectively. The use of valproic acid decreased CL/F by 38.5%, whereas the co-administration of rifampicin caused an increase in CL/F of 64.7%. The CL/F decreased by 52.5% in SLC22A1 -1222AA carriers. Patients with the ABCG2 -34AA genotype had a 42.0% decrease in V/F, whereas patients with the MDR1 -2677TT and C3435TT genotypes had a 136% increase in V/F. No obvious genetic effect of UGT enzymes was found relative to the concentrations of LTG in Chinese patients. Recommended dose regimens for patients with different gene polymorphisms and comedications were estimated on the basis of Monte Carlo simulations and the established model. These findings should be valuable for developing individualized dosage regimens in adult and adolescent Chinese patients 13–65 years of age.

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Section: Introductionmentioning

confidence: 99%

Effects of Comedication and Genetic Factors on the Population Pharmacokinetics of Lamotrigine: A Prospective Analysis in Chinese Patients With Epilepsy

et al. 2019

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“…Multiple variations with functional consequences, including M420del ( SLC22A1*2 ), R61C ( SLC22A1*3 ), G401S ( SLC22A1*4 ), and G465R ( SLC22A1*5 ), are absent in East Asians, whereas they can reach frequencies up to 21.9% in other populations (Table 1). In contrast, L160F, which is associated with altered imatinib pharmacokinetics and an increased risk of resistance to imatinib (Cargnin et al 2018; Di Paolo et al 2014; Makhtar et al 2018), is common in East Asians (MAF = 14.2%) but lowest in Africans (3.8%).…”

Section: Resultsmentioning

confidence: 99%

The genetic landscape of the human solute carrier (SLC) transporter superfamily

Schaller

Lauschke

2019

Hum Genet

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The human solute carrier (SLC) superfamily of transporters is comprised of over 400 membrane-bound proteins, and plays essential roles in a multitude of physiological and pharmacological processes. In addition, perturbation of SLC transporter function underlies numerous human diseases, which renders SLC transporters attractive drug targets. Common genetic polymorphisms in SLC genes have been associated with inter-individual differences in drug efficacy and toxicity. However, despite their tremendous clinical relevance, epidemiological data of these variants are mostly derived from heterogeneous cohorts of small sample size and the genetic SLC landscape beyond these common variants has not been comprehensively assessed. In this study, we analyzed Next-Generation Sequencing data from 141,456 individuals from seven major human populations to evaluate genetic variability, its functional consequences, and ethnogeographic patterns across the entire SLC superfamily of transporters. Importantly, of the 204,287 exonic single-nucleotide variants (SNVs) which we identified, 99.8% were present in less than 1% of analyzed alleles. Comprehensive computational analyses using 13 partially orthogonal algorithms that predict the functional impact of genetic variations based on sequence information, evolutionary conservation, structural considerations, and functional genomics data revealed that each individual genome harbors 29.7 variants with putative functional effects, of which rare variants account for 18%. Inter-ethnic variability was found to be extensive, and 83% of deleterious SLC variants were only identified in a single population. Interestingly, population-specific carrier frequencies of loss-of-function variants in SLC genes associated with recessive Mendelian disease recapitulated the ethnogeographic variation of the corresponding disorders, including cystinuria in Jewish individuals, type II citrullinemia in East Asians, and lysinuric protein intolerance in Finns, thus providing a powerful resource for clinical geneticists to inform about population-specific prevalence and allelic composition of Mendelian SLC diseases. In summary, we present the most comprehensive data set of SLC variability published to date, which can provide insights into inter-individual differences in SLC transporter function and guide the optimization of population-specific genotyping strategies in the bourgeoning fields of personalized medicine and precision public health.Electronic supplementary materialThe online version of this article (10.1007/s00439-019-02081-x) contains supplementary material, which is available to authorized users.

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“…IM is a well-known, orally administered tyrosine kinase inhibitor (TKI) (Musumeci et al, 2015). The bioavailability of IM is ∼90% via the oral route, as it is metabolized predominantly by cytochrome P450 enzymes (Musumeci et al, 2015), CYP3A4 (Maddin et al, 2016), and CYP3A5 (Cargnin et al, 2018), to its major circulating active metabolite, N-desmethyl imatinib (NDI)/ CGP74588 (Lin et al, 2019). This metabolite also binds to the ATP binding pocket of the tyrosine kinase domain (Josephs et al, 2013).…”

Section: Current Usage Of Imatinib Mesylate For Gastrointestinal Stromentioning

confidence: 99%

“…Administration of drugs along with IM in GIST therapy is common. As mentioned earlier, IM is metabolized predominantly in the liver by cytochromes CYP3A4 and CYP3A5 (Widmer et al, 2018), and it is mainly transported and excreted into bile by transporters related to P-glycoprotein (P-gp) (Maia et al, 2018). Hence, combining IM with a CYP inducer, CYP inhibitor, or a P-gp agonist would affect the plasma levels of IM.…”

Section: Imatinib Mesylate-drug Interactionsmentioning

confidence: 99%

Factors Influencing the Steady-State Plasma Concentration of Imatinib Mesylate in Patients With Gastrointestinal Stromal Tumors and Chronic Myeloid Leukemia

et al. 2020

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Imatinib mesylate (IM) is the standard treatment for advanced, metastatic gastrointestinal stromal tumors (GISTs) and chronic myeloid leukemia (CML) with a fixed daily standard dosage via the oral route. Interindividual and intraindividual variability in plasma concentrations have been closely linked to the efficacy of IM therapy. Therefore, this review identifies and describes the key factors influencing the plasma concentration of IM in patients with GISTs and CML. We used the following keywords to search the PubMed, EMBASE, Ovid, Wangfang, and CNKI databases to identify published reports: IM, plasma concentration, GISTs, CML, drug combination/interaction, pathology, and genotype/genetic polymorphism, either alone or in combination. This literature review revealed that only 10 countries have reported the mean concentrations of IM in GISTs or CML patients and the clinical outcomes in different ethnic groups and populations. There were totally 24 different gene polymorphisms, which were examined for any potential influence on the steady-state plasma concentration of IM. As a result, some genotype locus made discrepant conclusion. Herein, the more sample capacity, multicenter, long-term study was worthy to carry out. Eleven reports were enumerated on clinical drug interactions with IM, while there is not sufficient information on the pharmacokinetic parameters altered by drug combinations with IM that could help in investigating the actual drug interactions. The drug interaction with IM should be paid more attention in the future research.

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Impact of SLC22A1 and CYP3A5 genotypes on imatinib response in chronic myeloid leukemia: A systematic review and meta-analysis

Cited by 21 publications

References 41 publications

Effects of Comedication and Genetic Factors on the Population Pharmacokinetics of Lamotrigine: A Prospective Analysis in Chinese Patients With Epilepsy

Effects of Comedication and Genetic Factors on the Population Pharmacokinetics of Lamotrigine: A Prospective Analysis in Chinese Patients With Epilepsy

The genetic landscape of the human solute carrier (SLC) transporter superfamily

Factors Influencing the Steady-State Plasma Concentration of Imatinib Mesylate in Patients With Gastrointestinal Stromal Tumors and Chronic Myeloid Leukemia

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