Pharmacokinetics of gallic acid and protocatechuic acid in humans after dosing with Relinqing (RLQ) and the potential for RLQ-perpetrated drug-drug interactions on organic anion transporter (OAT) 1/3.
Pharm Biol
; 59(1): 757-768, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34144662
ABSTRACT
CONTEXT Relinqing granules (RLQ) are being used alone or in combination with antibacterial drugs to treat urological disorders. OBJECTIVE:
This study investigates the pharmacokinetics of RLQ in humans and the potential for RLQ-perpetrated interactions on transporters. MATERIALS ANDMETHODS:
Twelve healthy subjects (six women and six men) participated to compare single- and multiple-dose pharmacokinetics of RLQ. In the single-dose study, all 12 subjects received 8 g of RLQ orally. After a 7-d washout period, the subjects received 8 g of RLQ for seven consecutive days (t.i.d.) and then a single dose. Gallic acid (GA) and protocatechuic acid (PCA) in plasma and urine samples were analysed using LC-MS/MS. The transfected cells were used to study the inhibitory effect of GA (50-5000 µg/L) and PCA (10-1000 µg/L) on transporters OAT1, OAT3, OCT2, OATP1B1, P-gp and BCRP.RESULTS:
GA and PCA were absorbed into the blood within 1 h after administration and rapidly eliminated with a half-life of less than 2 h. The mean peak concentrations of GA (102 and 176 µg/L) and PCA (4.54 and 7.58 µg/L) were lower in males than females, respectively. The 24 h urine recovery rates of GA and PCA were about 10% and 5%, respectively. The steady-state was reached in 7 d without accumulation. GA was a potent inhibitor of OAT1 (IC50 = 3.73 µM) and OAT3 (IC50 = 29.41 µM), but not OCT2, OATP1B1, P-gp or BCRP. DISCUSSION ANDCONCLUSIONS:
GA and PCA are recommended as PK-markers in RLQ-related pharmacokinetic and drug interaction studies. We should pay more attention to the potential for RLQ-perpetrated interactions on transporters.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Medicamentos de Ervas Chinesas
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Transportadores de Ânions Orgânicos Sódio-Independentes
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Proteína 1 Transportadora de Ânions Orgânicos
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Interações Medicamentosas
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Ácido Gálico
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Hidroxibenzoatos
Limite:
Adult
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Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article