loratadine, Claritin
Impact of interventions designed to increase market share and prescribing of fexofenadine at HMOs.

Benedetto SR, Sloan AS, Duncan BS.

Advance Paradigm Clinical Services (APCS), Hunt Valley, MD 21031, USA. sbenedet apclinical.com

The impact of interventions designed to shift prescribing from loratadine to fexofenadine at HMOs was studied. Pharmacy claims data for a six-month preintervention period at four HMOs were analyzed to identify all new and refill prescriptions for loratadine, fexofenadine, astemizole, and cetirizine. The interventions consisted of a mandatory lockout of loratadine in favor of fexofenadine (at HMO A), a voluntary switch to fexofenadine promoted through letters to both physicians and members (HMO B), and a voluntary switch promoted through letters to physicians only (HMO C). There was no intervention at HMO D. Pharmacy claims data for the six months after each intervention program was implemented were analyzed to determine changes in the market share and prescribing of the study drugs. After the intervention programs were implemented, the market share of fexofenadine increased from 18.9% to 65.2% at HMO A, from 14.8% to 21.0% at HMO B, and from 20.7% to 23.8% at HMO C. Loratadine's market share decreased from 62.3% to 8.7% at HMO A, from 67.5% to 58.6% at HMO B, and from 70.5% to 65.3% at HMO C. HMOs A, B, and C each had greater shifts in market share for fexofenadine and loratadine than the control HMO. Changes in prescribing followed a similar pattern for the 25 physicians at each HMO who had most frequently prescribed loratadine during the preintervention period. The average cost per antihistamine prescription decreased 22.3% at HMO A. Prescription costs continued to rise at HMOs B, C, and D. Mandating the use of fexofenadine produced a significant increase in its market share, reduced the cost of nonsedating antihistamines, and successfully influenced prescribing behavior. Voluntary programs had a more modest impact on market share and did not stop increases in prescription costs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11030030&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Second-derivative spectrophotometric assay of pseudoephedrine, ibuprofen and loratadine in pharmaceuticals.

Ivanovic D, Medenica M, Markovic S, Mandic G.

Institute of Pharmaceutical Chemistry and Drug Analysis, Belgrade, Yugoslavia.

In this paper the second-derivative spectrophotometric method for the simultaneous determination of pseudoephedrine (CAS 90-82-4) in the combinations with ibuprofen (CAS 15687-27-1) and loratadine (CAS 79794-75-5) is described. Optimal conditions for the quantitative analysis of coated tablets (Test I) and tablets (Test II) were settled. The second-derivative order of the spectra in ethanol with the wavelength modulation was used. For the quantitative assay for all of the investigated substances in the laboratory mixture or in respective pharmaceutical dosage forms the "zero-crossing" technique was applied. The authors propose this second-derivative spectrophotometry for a rapid, simple, precise and accurate determination of the mentioned tests or a corresponding multicomponent mixture.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11148855&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Desloratadine: A new, nonsedating, oral antihistamine.

Geha RS, Meltzer EO.

Boston Children's Hospital and Harvard Medical School, Enders Building, Room 809, 300 Longwood Ave., Boston, MA 02115, USA.

Desloratadine is a new, selective, H(1)-receptor antagonist that also has anti-inflammatory activity. In vitro studies have shown that desloratadine inhibits the release or generation of multiple inflammatory mediators, including IL-4, IL-6, IL-8, IL-13, PGD(2), leukotriene C(4), tryptase, histamine, and the TNF-alpha-induced chemokine RANTES. Desloratadine also inhibits the induction of cell adhesion molecules, plateletactivating factor-induced eosinophil chemotaxis, TNF-alpha-induced eosinophil adhesion, and spontaneous and phorbol myristate acetate-induced superoxide generation in vitro. In animals desloratadine had no effect on the central nervous, cardiovascular, renal, or gastrointestinal systems. Desloratadine is rapidly absorbed, has dose-proportional pharmacokinetics, and has a half-life of 27 hours. The absorption of desloratadine is not affected by food, and the metabolism and elimination are not significantly affected by the subject's age, race, or sex. There are no clinically relevant interactions between desloratadine and erythromycin, ketoconazole, or grapefruit juice. Desloratadine is not a significant substrate of the P-glycoprotein transport system. Once daily administration of desloratadine rapidly reduces the nasal and nonnasal symptoms of seasonal allergic rhinitis, including congestion. In patients with seasonal allergic rhinitis and concomitant asthma, desloratadine treatment was also associated with significant reductions in total asthma symptom score and use of inhaled beta(2)-agonists. Use of desloratadine in patients with chronic idiopathic urticaria was associated with significant reductions in pruritus, number of hives, size of the largest hive, and interference with sleep and daily activities. Clinical experience in over 2300 patients has shown that the adverse event profile of desloratadine is similar to that of placebo; desloratadine has no clinically relevant effects on electrocardiographic parameters, does not impair wakefulness or psychomotor performance, and does not exacerbate the psychomotor impairment associated with alcohol use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11295678&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Evaluation of a four-channel multiplexed electrospray triple quadrupole mass spectrometer for the simultaneous validation of LC/MS/MS methods in four different preclinical matrixes.

Yang L, Mann TD, Little D, Wu N, Clement RP, Rudewicz PJ.

Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033-1300, USA.

A four-channel multiplexed electrospray interface on a triple quadrupole mass spectrometer was evaluated for the simultaneous validation of LC/MS/MS methods for the quantitation of loratadine and its metabolite, descarboethoxyloratadine, in four different biological matrixes. The assays were performed in rat, rabbit, mouse, and dog plasma from 1 to 1000 ng/mL using 96-well solid-phase extraction for sample preparation. The limit of quantitation of 1 ng/mL corresponded to 5.56 pg of each analyte injected on-column. For the drug, quality control samples (n = 6 at four concentrations) had precision ranging from 0.967 to 16.0% and accuracy ranging from -8.44 to 10.5% across all four species. For the metabolite, the precision ranged from 0.684 to 11.0% and the accuracy was between 6.36 and -9.06%. Intersprayer cross talk for the multiplexed electrospray ion source was evaluated as a function of analyte concentration and was less than 0.08% at concentrations as high as 1000 ng/mL. These results demonstrate the feasibility of using parallel analysis to reduce the time required for method validation and to increase sample throughput in drug development studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11338587&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Sensitive liquid chromatography-tandem mass spectrometry method for the determination of loratadine and its major active metabolite descarboethoxyloratadine in human plasma.

Sutherland FC, de Jager AD, Badenhorst D, Scanes T, Hundt HK, Swart KJ, Hundt AF.

FARMOVS Research Centre for Clinical Pharmacology and Drug Development, University of Orange Free State, Bloemfontein, South Africa. gnfmfcws frm.uovs.ac.za

A sensitive method for the simultaneous determination of loratadine and its major active metabolite descarboethoxyloratadine (DCL) in plasma was developed, using high-performance liquid chromatographic separation with tandem mass spectrometric detection. The samples were extracted from plasma with toluene followed by back-extraction into formic acid (2%) for DCL after which the toluene containing the loratadine was evaporated, the analyte reconstituted and combined with the DCL back-extract. Chromatography was performed on a Phenomenex Luna C18 (2) 5-microm, 150x2.1-mm column with a mobile phase consisting of acetonitrile-0.1% formic acid using gradient elution (10 to 90% acetonitrile in 2 min) at a flow-rate of 0.3 ml/min. Detection was achieved by a Perkin-Elmer API 2000 mass spectrometer (LC-MS-MS) set at unit resolution in the multiple reaction monitoring mode. TurbolonSpray ionisation was used for ion production. The mean recovery for loratadine and descarboethoxyloratadine was 61 and 100%, respectively, with a lower limit of quantification at 0.10 ng/ml for both the analyte and its metabolite. This is the first assay method described for the simultaneous determination of loratadine and descarboethoxyloratadine in plasma using one chromatographic run. The method is sensitive and reproducible enough to be used in pharmacokinetic studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11358228&dopt=Abstract loratadine, Claritin



loratadine, Claritin
Polarographic behaviour of loratadine and its direct determination in pharmaceutical formulation and human plasma by cathodic adsorptive stripping voltammetry.

Ghoneim MM, Mabrouk MM, Hassanein AM, Tawfik A.

Chemistry Department, Faculty of Science, Tanta University, 31527, Tanta, Egypt. mghoneim cic.com.eg

The polarographic behaviour of the antihistaminic drug loratadine has been investigated in B.R. buffer solution of different pH values. Contradictory to that mentioned before in a previously published work, loratadine is electro-active at the mercury electrode. In B.R. buffer solution of pH values > or =6 it is reduced via a single 2-electrons irreversible wave corresponding to saturation of carbon-nitrogen double bond of the pyridine ring. The electrode reaction pathway was proposed and discussed. A sensitive differential pulse stripping voltammetric method based on controlled adsorptive accumulation of loratadine on a hanging mercury drop electrode has been developed for its direct determination at nanomolar concentrations without nitration of the drug. The optimized conditions for the direct cathodic adsorptive stripping voltammetric determination of the drug are: 0.1 M sodium hydroxide solution as a supporting electrolyte, accumulation potential, -1.2 V; accumulation time, 30 s; scan rate, 2-5 mV x s(-1) and pulse amplitude 100 mV. The proposed procedure was applied for the assay of loratadine in pharmaceutical formulation and human plasma. The average recoveries were 99.32-99.44 and 100.33-102.99% with the RSD 0.27-0.42 and 0.39-0.90% in pharmaceutical formulation and human plasma, respectively. The limits of detection of 1.60x10(-7) and 1.25x10(-7) M loratadine were found in pharmaceutical formulation and human plasma, respectively.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11377076&dopt=Abstract loratadine, Claritin