ArticleDrug metabolism and disposition: the biological fate of chemicals2012
γ-Hydroxybutyrate blood/plasma partitioning: effect of physiologic pH on transport by monocarboxylate transporters.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Sex and Cross-Sex Testosterone Treatment Alters Gamma-Hydroxybutyrate Acid Toxicokinetics and Toxicodynamics in Rats.Pharmaceutics · 2024Article
- GHB toxicokinetics and renal monocarboxylate transporter expression are influenced by the estrus cycle in rats.BMC pharmacology & toxicology · 2023Article
- γ-Hydroxybutyric Acid: Pharmacokinetics, Pharmacodynamics, and Toxicology.The AAPS journal · 2021Review
- Monocarboxylate Transporters (SLC16): Function, Regulation, and Role in Health and Disease.Pharmacological reviews · 2020Review
- Monocarboxylate Transporter 1 (MCT1) in Liver Pathology.International journal of molecular sciences · 2020Article
- Effects of renal impairment on transporter-mediated renal reabsorption of drugs and renal drug-drug interactions: A simulation-based study.Biopharmaceutics & drug disposition · 2018Article
- The Drug of Abuse Gamma-Hydroxybutyric Acid Exhibits Tissue-Specific Nonlinear Distribution.The AAPS journal · 2017Article
- Article
- γ-Hydroxybutyric Acid (GHB) Pharmacokinetics and Pharmacodynamics: Semi-Mechanistic and Physiologically Relevant PK/PD Model.The AAPS journal · 2017Article
- In Vivo and In Vitro Evidence for Brain Uptake of 4-Phenylbutyrate by the Monocarboxylate Transporter 1 (MCT1).Pharmaceutical research · 2016Article
- Semi-mechanistic kidney model incorporating physiologically-relevant fluid reabsorption and transporter-mediated renal reabsorption: pharmacokinetics of γ-hydroxybutyric acid and L-lactate in rats.Journal of pharmacokinetics and pharmacodynamics · 2015Article
- A Novel Monocarboxylate Transporter Inhibitor as a Potential Treatment Strategy for γ-Hydroxybutyric Acid Overdose.Pharmaceutical research · 2015Article
- GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome.Current neuropharmacology · 2015Review
- Mechanistic modeling of monocarboxylate transporter-mediated toxicokinetic/toxicodynamic interactions between γ-hydroxybutyrate and L-lactate.The AAPS journal · 2014Article
- Role of monocarboxylate transporters in drug delivery to the brain.Current pharmaceutical design · 2014Review
- Brain extracellular γ-hydroxybutyrate concentrations are decreased by L-lactate in rats: role in the treatment of overdoses.Pharmaceutical research · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The drug of abuse γ-hydroxybutyrate (GHB) displays nonlinear renal clearance, which has been attributed to saturable renal reabsorption by monocarboxylate transporters (MCTs) present in the kidney. MCT1 is also present in red blood cells (RBCs); however, the significance of this transporter on the blood/plasma partitioning of GHB is unknown. The purpose of this research was to characterize the transport of GHB across the RBC membrane and assess GHB blood/plasma partitioning in vivo in the presence and absence of a competitive MCT inhibitor, l-lactate. In vitro experiments were performed using freshly isolated rat erythrocytes at pH values of 6.5 and 7.4. Inhibition with p-chloromercuribenzene sulfonate and 4,4'-diisothiocyanostilbene-2,2'-disulfonate were used to determine the contribution of MCT1 and band 3, respectively, on GHB uptake. For in vivo experiments, rats were administered GHB (400-1500 mg/kg) with and without l-lactate. In vitro experiments demonstrated that GHB is transported across the RBC membrane primarily by MCT1 at relevant in vivo concentrations. The K(m) for MCT1 was lower at pH 6.5 than that at pH 7.4, 2.2 versus 17.0 mM, respectively. The in vivo blood/plasma partitioning of GHB displayed linearity across all concentrations. l-Lactate coadministration increased GHB renal clearance but had no effect on the blood/plasma ratio. Unlike its MCT-mediated transport in the intestine and kidneys, GHB blood/plasma partitioning appears to be linear and is unaffected by l-lactate. These findings can be attributed, at least in part, to differences in physiologic pH at different sites of MCT-mediated transport.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.