loratadine, Claritin
Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of 3-hydroxydesloratadine.

Ghosal A, Yuan Y, Hapangama N, Su AD, Alvarez N, Chowdhury SK, Alton KB, Patrick JE, Zbaida S.

Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA. anima.ghosal spcorp.com

Desloratadine is a non-sedating antihistamine recently approved for the treatment of seasonal allergic rhinitis. The major metabolite of desloratadine in human plasma and urine is the glucuronide conjugate of 3-hydroxydesloratadine. 3-Hydroxydesloratadine-glucuronide is also the major in vitro metabolite of 3-hydroxydesloratadine formed by incubation of 3-hydroxydesloratadine with human liver microsomes supplemented with uridine 5'-diphosphate-glucuronic acid (UDPGA). The metabolite structure was confirmed by LC-MS and LC-MS/MS. Out of ten recombinant human UDP-glucuronosyltransferases (UGTs), UGT1A1, UGT1A3, UGT1A8 and UGT2B15 exhibited catalytic activity with respect to the formation of 3-hydroxydesloratadine-glucuronide. Inhibition studies with known inhibitors of UGT (diclofenac, flunitrazepam and bilirubin) confirmed the involvement of UGT1A1, UGT1A3 and UGT2B15 in the formation of 3-hydroxydesloratadine-glucuronide. The results from this study demonstrated that the in vitro formation of 3-hydroxydesloratadine-glucuronide from 3-hydroxydesloratadine was mediated via UGT1A1, UGT1A3 and UGT2B15 in human liver.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15334623&dopt=Abstract loratadine, Claritin



loratadine, Claritin
[Analysis of tablets containing the antihistamine loratadine: a contribution to the identification of impurities]

[Article in Czech]

Issa N, Mlynarova M.

Statny ustav pre kontrolu lieciv, Bratislava.

Thin-layer chromatography on silica gel (Merck) was employed to examine potential impurities present in loratadine-containing tablets. A method usable for testing of impurities was elaborated, which suitably supplements the determination of loratadine content using the spectrophotometric method in the UV region. The method was validated for selected pharmaceuticals.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15369231&dopt=Abstract loratadine, Claritin



loratadine, Claritin
The economic impact of payer policies after the Rx-to-OTC switch of second-generation antihistamines.

Sullivan PW, Nichol MB.

Pharmaceutical Outcomes Research Program, University of Colorado School of Pharmacy, Denver, CO 80262, USA. Patrick.Sullivan UCHSC.edu

OBJECTIVE: As a result of the over-the-counter (OTC) introduction of loratadine, health plans have been struggling to determine the best policy to incorporate this change within their existing drug benefit structure for second-generation antihistamines (SGA). The objective of this study was to examine the economic impact of payer policies in response to the Rx-to-OTC switch of loratadine. STUDY DESIGN: Decision analysis was used to model the budgetary impact and cost-effectiveness of four policies for SGA benefits for the managed care organization (MCO), employer, and Medicaid perspectives separately. PATIENTS AND METHODS: Outcomes included direct medical costs and lost productivity (employers only), discounted, quality-adjusted life-years (QALYs) saved because of amelioration of allergic rhinitis symptoms and avoidance of unintentional injuries associated with the use of first-generation antihistamines (FGA). Bayesian probabilistic sensitivity analysis was conducted using second-order Monte Carlo simulation. RESULTS: Providing limited OTC and second-tier prescription benefits would cost approximately 0.13 dollars and 0.30 dollars compared to third-tier prescription benefits for employers and MCOs, respectively, and would save Medicaid 0.02 dollars per member per month (PMPM). Providing limited coverage for OTC loratadine while retaining second-tier prescription benefits for SGA was the optimal policy for a willingness to pay below 26,200 dollars per QALY for all payers. CONCLUSIONS: Offering second-tier prescription and limited OTC benefits provides greater effectiveness and is not significantly more expensive PMPM than discontinuation. Some of the drug savings from limiting coverage of prescription SGA may be attenuated by the cost of lost productivity and direct medical expenditures due to unintentional injuries associated with increased FGA use in addition to the increased cost of therapeutic substitutes.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15449632&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Classification of loratadine based on the biopharmaceutics drug classification concept and possible in vitro-in vivo correlation.

Khan MZ, Rausl D, Zanoski R, Zidar S, Mikulcic JH, Krizmanic L, Eskinja M, Mildner B, Knezevic Z.

PLIVA Research Institute Ltd, Zagreb, Croatia. Zahir.Khan pliva.com

Loratadine was studied both in vitro and in vivo (in healthy humans) to classify it according to the Biopharmaceutics Classification System (BCS) in order to gain more understanding of the reasons for its highly variable nature with respect to plasma time profiles, and to determine the most appropriate dissolution test conditions for in vitro assessment of the release profile of the drug from solid dose forms. Based on the solubility of loratadine determined under various pH conditions and its permeability through Caco-2 monolayers, loratadine was classified as a Class II drug. Plasma profiles were predicted by convolution analysis using dissolution profiles obtained under various pH and hydrodynamic conditions as the input function and plasma time data obtained from a syrup formulation as the weighting function. The predicted profiles based on dissolution studies done at gastric pH values were in reasonable agreement with the mean bio-data suggesting dissolution testing should be done at gastric pH values. However, the bio-data were highly variable and it is suggested this may be due, at least in part, to high individual gastric pH variability and dissolution occurring in the intestine on some occasions, and therefore, dissolution testing should also be done in simulated intestinal fluid.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15467209&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Desloratadine partially inhibits the augmented bacterial responses in the sinuses of allergic and infected mice.

Kirtsreesakul V, Blair C, Yu X, Thompson K, Naclerio RM.

Department of Surgery, Section of Otolaryngology-Head and Neck Surgery, The University of Chicago, Chicago, IL 60637, USA.

BACKGROUND: Allergic rhinitis (AR) is considered a major predisposing factor for the development of acute bacterial rhinosinusitis. How AR augments a bacterial infection is unknown. OBJECTIVE: Our purpose in this study was to test whether an H1 receptor antagonist, desloratadine, could reduce the augmented effect of an ongoing allergic reaction on acute bacterial rhinosinusitis. METHODS: Three groups of infected and ovalbumin (OVA)-sensitized mice were studied: (1) infected and allergic mice treated with desloratadine, (2) infected and allergic mice treated with placebo, and (3) infected mice. A fourth group of uninfected, non-sensitized mice served as a control for the cellular changes. BALB/c mice were sensitized by two intraperitoneal injections of OVA given 8 days apart. One day after the second injection, the mice were nasally exposed daily to 6% OVA (the groups treated with desloratadine or placebo) or phosphate-buffered saline (PBS) (the infection-only group) for 5 days. After the second OVA exposure, the mice were intranasally inoculated with Streptococcus pneumoniae. Desloratadine or placebo was given daily throughout the OVA exposure period. Nasal allergic symptoms were observed by counting of nasal rubbing and sneezing for 10 min after OVA or PBS nasal challenge. On day 5 post-infection, nasal lavage culture was done, and the inflammatory cells in the sinuses were evaluated by flow cytometry. RESULTS: Mice that were made allergic, infected, and treated with placebo showed more organisms and phagocytes than did only infect mice. They also manifested allergic nasal symptoms and eosinophil influx into the sinuses. Desloratadine treatment during allergen exposure reduced allergic symptoms and reduced sinonasal infection (P<0.05). There tended to be less myeloid cell and neutrophil influx (P=0.09 both), but not eosinophil influx (P=0.85) compared with that in the placebo-treated group. CONCLUSION: Desloratadine treatment during nasal challenge inhibited allergic symptoms and reduced sinonasal infection, suggesting that histamine via an H1 receptor plays a role in the augmented infection in mice with an ongoing allergic reaction.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15479283&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Differential IL-10 receptor gene expression in acute versus chronic atopic eczema. Modulation by immunosuppressive drugs and cytokines in normal cultured keratinocytes.

Muschen A, Mirmohammadsadegh A, Jarzebska-Deussen B, Abts HF, Ruzicka T, Michel G.

Department of Dermatology, Heinrich-Heine-University Dusseldorf, Germany.

OBJECTIVE AND DESIGN: The effects of the anticytokine interleukin 10 (IL-10) are mediated by specific receptors. In this study we examined the role of the IL-10 receptor (IL-10R) in the pathophysiology of atopic eczema. MATERIALS AND METHODS: For this purpose we analyzed the expression of IL-10R in the skin of patients with acute and chronic atopic eczema in comparison to the expression in healthy individuals using in situ binding experiments with fluorescently labeled IL-10 and semiquantitative reverse transcriptase-PCR specific for IL-10R1. In addition, we studied the influence of the Th2-associated cytokine interleukin-4 (IL-4), the Th1-associated gamma-interferon (IFN-gamma), the immunosuppressive drug FK506, the H1-antagonist loratadine and UVA irradiation on the expression of IL-10R1 in cultured normal human keratinocytes. RESULTS: We found that IL-10 receptor mRNA and protein are strongly downregulated in acute phase atopic lesions. Furthermore we could show that IL-4, IFN-gamma, FK506, loratadine and UVA enhance the mRNA levels of the IL-10R1 in vitro in normal cultured keratinocytes. We could also demonstrate restored IL-10R1 mRNA levels in lesional atopic skin of a patient after UVA1 therapy. CONCLUSIONS: Our results demonstrate for the first time that IL-10 receptors may have a role in the pathogenesis of atopic eczema and its upregulation by FK506 and UVA could explain the therapeutic efficacy of these agents.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10563471&dopt=Abstract loratadine, Claritin