ABSTRACT
This study aimed to evaluate the effects of green tea on the pharmacokinetics and pharmacodynamics of the ß-blocker nadolol. Ten healthy volunteers received a single oral dose of 30 mg nadolol with green tea or water after repeated consumption of green tea (700 ml/day) or water for 14 days. Catechin concentrations in green tea and plasma were determined. Green tea markedly decreased the maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC(0-48)) of nadolol by 85.3% and 85.0%, respectively (P < 0.01), without altering renal clearance of nadolol. The effects of nadolol on systolic blood pressure were significantly reduced by green tea. [(3)H]-Nadolol uptake assays in human embryonic kidney 293 cells stably expressing the organic anion-transporting polypeptides OATP1A2 and OATP2B1 revealed that nadolol is a substrate of OATP1A2 (Michaelis constant (K(m)) = 84.3 µmol/l) but not of OATP2B1. Moreover, green tea significantly inhibited OATP1A2-mediated nadolol uptake (half-maximal inhibitory concentration, IC(50) = 1.36%). These results suggest that green tea reduces plasma concentrations of nadolol possibly in part by inhibition of OATP1A2-mediated uptake of nadolol in the intestine.
Subject(s)
Adrenergic beta-Antagonists/pharmacokinetics , Catechin/pharmacokinetics , Food-Drug Interactions , Nadolol/pharmacokinetics , Tea/chemistry , Adrenergic beta-Antagonists/pharmacology , Adult , Area Under Curve , Blood Pressure/drug effects , Cross-Over Studies , Female , HEK293 Cells , Humans , Inhibitory Concentration 50 , Intestinal Mucosa/metabolism , Male , Nadolol/pharmacology , Organic Anion Transporters/metabolism , Young AdultABSTRACT
OBJECTIVES: To determine the presence or extent of arginine deficiency in pressure ulcer (PU) patients on percutaneous endoscopic gastrostomy (PEG) feeding and to examine the effects of arginine supplementation on PU healing. DESIGN: All eligible PEG patients, with and without PU, were cross-sectionally assessed for plasma arginine. Three-month supplementation with arginine-enriched water (Arginaid Water) was performed on a subset of patients with PU. This intervention study was a prospective, non-controlled trial with 5 PU patients. SETTING: Geriatric ward of a rural clinical hospital in Japan. PARTICIPANTS: Thirty-nine inpatients with PEG feeding were assessed for plasma arginine. Five of the 13 patients with PU and five of 26 patients without PU underwent amino acid profiling. INTERVENTION: Five of the patients with PU received Arginaid Water supplementation. MEASUREMENTS: Plasma amino acid measurements and biochemical analyses were performed. For those with PU on Arginaid Water supplementation, plasma arginine concentration and PU status were monitored every month. RESULTS: Patients with PU showed significantly lower plasma arginine concentration compared to those without PU (control vs. PU; 80.2±21.3 vs 62.8±14.7 nmol/ml, p<0.01). After the addition of Arginaid Water, plasma arginine concentration increased (before vs 3 months later; 57.9±1.8 vs 83.1±8.5, p<0.01), and PU area, perimeter, DESIGN-R and PUSH scores significantly improved. CONCLUSION: Plasma arginine was lower in PEG patients with PU. The healing rate of PU is improved with Arginaid Water supplementation. The findings from this study support the use of arginine supplementation in PEG patients with PU.