• Biomolecules & Therapeutics
• /
• 제17권2호
• /
• pp.205-210
• /
• 2009

The present study investigated the effects of hydrocortisone on the pharmacokinetics of loratadine in rats after intravenous and oral administration. A single dose of loratadine was administered either orally (4 mg/kg) or intravenously (1 mg/kg) with or without oral hydrocortisone (0.3 or 1.0 mg/kg). Compared to the control group (without hydrocortisone), after oral administration of loratadine, the area under the plasma concentration-time curve (AUC) was significantly increased by 30.2-81.7% in the presence of hydrocortisone (p<0.05). The peak plasma concentration ($C_{max}$) was significantly increased by 68.4% in the presence of 1.0 mg/kg hydrocortisone after oral administration of loratadine (p<0.05). Hydrocortisone (1.0 mg/kg) significantly increased the terminal plasma half-life ($t_{1/2}$) of loratadine by 20.8% (p<0.05). Consequently, the relative bioavailability of loratadine was increased by 1.30- to 1.82-fold. In contrast, oral hydrocortisone had no effects on any pharmacokinetic parameters of loratadine given intravenously. This suggests that hydrocortisone may improve the oral bioavailability of loratadine by reducing first-pass metabolism of loratadine, most likely mediated by P-gp and/or CYP3A4 in the intestine and/or liver. In conclusion, hydrocortisone significantly enhanced the bioavailability of orally administered loratadine in rats, which may have been due to inhibition of both CYP 3A4-mediated metabolism and P-gp in the intestine and/or liver by the presence of hydrocortisone.

• Biomolecules & Therapeutics
• /
• 제19권3호
• /
• pp.364-370
• /
• 2011

The purpose of this study was to investigate the effects of curcumin on the pharmacokinetics of loratadine in rats. The effect of curcumin on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activity was evaluated. Pharmacokinetic parameters of loratadine were also determined after oral and intravenous administration in the presence or absence of curcumin. Curcumin inhibited CYP3A4 activity with an IC50 value of 2.71 ${\mu}M$ and the relative cellular uptake of rhodamine-123 was comparable. Compared to the oral control group, curcumin significantly increased the area under the plasma concentration-time curve and the peak plasma concentration by 39.4-66.7% and 34.2-61.5%. Curcumin also significantly increased the absolute bioavailability of loratadine by 40.0-66.1% compared to the oral control group. Consequently, the relative bioavailability of loratadine was increased by 1.39- to 1.67-fold. In contrast, curcumin had no effect on any pharmacokinetic parameters of loratadine given intravenously, implying that the enhanced oral bioavailability may be mainly due to increased intestinal absorption caused via P-gp and CYP3A4 inhibition by curcumin rather than to reduced renal and hepatic elimination of loratadine. Curcumin enhanced the oral bioavailability of loratadine in this study. The enhanced bioavailability of loratadine might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced fi rst-pass metabolism of loratadine via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by curcumin.

• 한국임상수의학회지
• /
• 제19권2호
• /
• pp.186-190
• /
• 2002

아토피성 피부염은 면역계재성 피부질환으로 소양증이 주요 증상이며 이의 치료가 필수적이다. 따라서 개에서 제2세대 항히스타민제의 임상적용을 위해 피부에 히스타민에 의해 유발된 팽진과 발적에 대한 loratadine, cetirizine과 terfenadine의억제 효과를 비교하였다. 3종의 항히스타민제는 대조군에 비해 매우 유의하게 발적반응을 억제하였으며(p<0.01) cetirizine이 다른 제제에 비해 높은 억제효과를 보였다. 3종의 항히스타민제는 팽진 반응을 억제하는 효과를 보였으며 loratadine의 억제효과가 일정하며 지속적이었다. 따라서 제 2세대 항히스타민제인 loratadine과 cetirizine은 개에서 아토피성 피부염의 소양증 치료에 적용할 수 있는 항히스타민제로 사료된다. 특히 스테로이드제제를 대체할 수 있는 치료효과를 보일 것으로 판단된다.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
• /
• pp.420.2-421
• /
• 2002

A validated UV determination of loratadine in human plasma was developed and the pharmacokinetic profiles of single dose of loratadine were determined in 8 healthy volunteers. Human serum samples (1.0 mL) spiked with known concentration of loratadine and 50 ng diazepam as an internal standard were alkalinized with 500 ${\mu}\ell$ ${\mu}\ell$ of 10% $Na_{2}CO_{3}$ and extracted with 7 mL of mixture of isopentane and hexane (2 : 1. v/v) for 5 min. Extracts were centrifuged and 6 mL of organic layer was back-extracted with 150 ${\mu}\ell$ of 12.5% $Na_{2}PO_{4}$ for 1 min. (omitted)

• 셀메드
• /
• 제8권1호
• /
• pp.5.1-5.4
• /
• 2018

Pharmacopuncture, or herbal acupuncture, is a new form of therapy derived from combinations of two traditional therapeutic methods, herbal medicine and acupuncture therapy. To compare the efficacy between loratadine-pharmacopuncture (LP) and loratadine-oral administration (LO), the effect of loratadine was investigated in murine models. Anti-anaphylactic effects of loratadine treatments were investigated in compound 48/80-induced systemic anaphylactic reaction and passive cutaneous anaphylaxis (PCA). LP treatment significantly inhibited the compound 48/80-induced systemic anaphylactic reaction and PCA. The effect between LP and LO were on a similar level. These results indicate that LP can be used as an alternative method for LO in case of emergency.

• 약학회지
• /
• 제43권5호
• /
• pp.642-651
• /
• 1999

Nonsedating antihistamines do net cause sedation in therapeutic doses because these drugs hardly cross the blood-brain barrier. Since most of the peripheral side dffects of conventional antihistamines are related to their muscarinic receptor blocking action, the present study was performed to investigate whether nonsedating antihistamines interact with the muscarinic receptors and discriminate the muscarinic receptor subtypes in the rat cerebral microsomal fraction which containes both $M_1,{\;}M_2,{\;}M_3{\;}and{\;}M_4$ receptors. Five nonsedating antihistamines at high concentrations inhibited [$^3H$]QNB binding to the muscarinic receptor in a dose-dependent manner. The inhibition curves of these drugs except loratadine which showed positive cooperativity (nH=1.55) were steep (nH=1), indicating interaction with a single homogenous population of the binding sites. Astemizole, clemizole and mequitazine increased the $K_D$ value for [$^3H$]QNB without affecting the binding site concentrations, and this increase in the $K_D$ value resulted from the ability of these drugs to slow [$^3H$]QNB-receptor association. The Ki values of astemizole, clemizole and mequitazine for the inhibition for the inhibition of [$^3H$]QNB binding to muscarinic receptor were 0.58, 5.99 and $0.007{\;}{\mu}M$, respectively. However, loratadine and terfenadine inhibited noncompetitively [$^3H$]QNB binding with the normalized $IC_50$ value of about $2{\;}{\mu}M$. These results demonstrate that; 1) astemizole, clemizole and mequitazine interact directly with the muscarinic receptor at high concentrations; 2) muscarinic receptor blocking potency of these drugs varies widely among drugs; 3) these drugs do not discriminate between muscarinic receptor subtypes.

• Bulletin of the Korean Chemical Society
• /
• 제27권2호
• /
• pp.291-294
• /
• 2006

A highly sensitive high-performance liquid chromatographic-tandem mass spectrometric method (HPLC-MSMS) has been developed to quantify itraconazole in human plasma for the purpose of pharmacokinetic studies. Sample preparation was carried out by liquid-liquid extraction using loratadine as an internal standard. Chromatographic separation used a YMC $C_{18}$ column, giving an extremely fast total run time of 3 min. The method was validated and used for the bioequivalence study of itraconazole tablets in healthy male volunteers (n = 31). The lower limit of detection proved to be 0.2 ng /mL for itraconazole.