The Distribution of Quetiapine and 7-Hydroxyquetiapine in Guinea Pig Hair Roots and Shafts after Repeated Administration: Exploration of the Mechanism of Drug Entry and Retention in Hair

Abstract

Abstract This study investigated the distribution of quetiapine and 7-hydroxyquetiapine in guinea pig hair roots and shafts after five repeated intragastric administrations at three doses (5, 10 and 25 mg/kg) by segmental analysis to explore the mechanism of drug entry and retention in hair. Hair root samples were collected after 7, 10, 14, 21, 28 and 35 d in area A after the first dose, and a hair shaft was plucked 35 d after the first dose. The maximum concentrations of quetiapine in hair roots in the low-, medium- and high-dose groups occurred at 50, 74 and 98 h after the first administration, and the maximum concentrations were 0.71 ng/mg (range: 0.54–0.84 ng/mg), 6.72 ng/mg (range: 4.59–9.75 ng/mg) and 12.72 ng/mg (range: 10.74–15.76 ng/mg), respectively. The maximum concentrations of 7-hydroxyquetiapine in the low-, medium- and high-dose groups were 0.67 ng/mg (0.23–1.15 ng/mg), 1.07 ng/mg (0.44–1.19 ng/mg) and 3.92 ng/mg (0.656.14 ng/mg), respectively, at 26 h. The maximum concentrations of quetiapine and 7-hydroxyquetiapine in hair roots were significantly positively correlated with the dose (n = 18; r2 = 0.84; P < 0.0001 for quetiapine and n = 18; r2 = 0.61; P = 0.0001 for 7-hydroxyquetiapine). The concentrations of quetiapine and 7-hydroxyquetiapine in hair roots were higher than those in hair shafts 10 d after administration, indicating drug and metabolite entry into the hair through the roots in the first few days after administration. The highest concentrations of quetiapine in the hair shaft in the low-, medium- and high-dose groups were found at the hair ends, and 7-hydroxyquetiapine in the hair shaft showed no obvious peak concentration. Combined with previous studies, we think, by analyzing the drug concentrations in the hair roots and shaft, that the most important way for drugs to enter into and be retained in hair is that the drug enters the hair through the blood circulation from hair root, then spreads and redistributes as the hair grows.