Delavirdine mesylate

Delavirdine mesylate is a member of the /7w(heteroaryl)piperazine (BHAP) class of nonnucleoside HIV-1 reverse transcriptase inhibitors (Adams et al., 1998 Romero et al., 1993 Romero, 1994). This class of compounds was discovered by Upjohn scientists from a computer-directed dissimilarity analysis of the Pharmacia Upjohn chemical library to select compounds for screening against HIV-1 RT. The result of the in vitro assay (Deibel et al., 1990) is an IC50 of 0.260 p,M, which is comparable to AZT. In accordance with the previous NNRTIs, delavirdine is a noncompetitive inhibitor of reverse transcriptase, and has a synergistic effect with nucleoside transcriptase and protease inhibitors (Chong et al., 1994). 

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) delavirdine mesylate efavirenz nevirapine... 

Morse GD, Fischl MA, Shelton MJ, Cox SR, Driver M, DeRemer M, Freimuth WW. Single-dose pharmacokinetics of delavirdine mesylate and didanosine in patients with human immunodeficiency virus infection. Antimicrob Agents Chemother 1997 41(l) 169-74. 

A different mechanism for dissolution slowing was reported for delavirdine mesylate tablets (81). In this direct compression formulation, the methane sulfonic acid from the drug was shown to react with the disintegrant croscarmellose sodium to form the free acid of croscarmellose and the poorly soluble delavirdine free base. The authors conclude that similar reactions could occur for any acid salt of a basic drug. 

Delavirdine mesylate Route Pregnancy Pharmacokinetic Rapidly... 

Counting polymorphs and solvatomorphs, delavirdine mesylate has been found in 12 different crystal forms, therefore presenting considerable difficulty in the determination of phase composition.63 Only through the combination of factor analysis with the quantitative IR technique could one develop a method useable in the characterization of research and production lots. The composition of drug lots consisting of mixtures of forms was identified through qualitative factor analysis, and quantitated using principal component analysis. Calibration models were developed for the determination of Form-VIII or Form-XH in Form-XI, and a standard error of prediction of 2.0% of either form was reported, with detection limits of 3-5%. 

When systems can form multiple anhydrate, hydrate, and solvate phases, the use of infrared spectroscopy can be extremely valuable. For example, depending on the recrystallization solvent, delavirdine mesylate has been found to form two anhydrous phases, two hydrates, an ethanol solvate, and an acetonitrile solvate, as well as six other phases resulting as the products of solid-state transformations of the hydrated and solvated phases [126], In this work, FTIR spectroscopy played an important role in working out the characterization of this system. 

In the solid-state NMR spectra of delavirdine mesylate, Form VIII shows a unique resonance at 17.3 ppm and Form XI a unique resonance at 20.2 ppm, while a resonance at 23.9 ppm is shared by both forms [157]. These spectral characteristics have been exploited for the development of a method to determine the Form VIII content in bulk Form XL As evident from the spectra shown in Fig. 12, the empirical limit of detection for the determination of Form VIII was approximately 2%. 

Solid-state nuclear magnetic resonance spectra obtained for Form XI of delavirdine mesylate, spiked with various levels of Form Vin. Spectra are shown for spiking levels of (1) 1%, (2) 2%, (3) 3%, (4) 5%, (5) 10%, and (6) 15%. (The figure was adapted from data contained in Ref. 157.)... 

However, there have been few studies focused on the quantitation of relative amounts of polymorphic forms. Solid-state CNMR was used to determine the amounts of carbamazepine anhydrate and dihydride [29] more recently the methodology of quantitative analysis was applied to delavirdine mesylate mixtures [30]. These works demonstrated that unambiguous identification of the polymorphic forms was possible with empirical detection limits about 2-3 %. 

Rescriptor (Delavirdine mesylate). Pfizer Inc. US Prescribing information, June 2006. 

Morse GD, Fischl MA, Cox SR, Thompsixi L, Della-Coletta AA, Freimuth WW. Effect of food on the steady-state (SS) phannacokinetics of delavirdine mesylate (DLV) in HIV+ patients. Intersci ConfAntimicr Agents Chemother 99S) 35,210. 

Borin MT, Chambers JH, Carel BJ, Gagnon S, Freimuth WW. Pharmacddnetic stutfy of the interaction between rifampin and delavirdine mesylate. ClinPharmacolTher( 9Sff)6, 544-... 

Morse GD, Adams JM, Shelton MJ, Hewitt RG, Cox SR, Chambers JH Gastric acidification increases delavirdine mesylate (DLV) exposure in HIV+ subjects with gastric hypoacidity (GH). Clin Pharmacol Ther( 996) 59,141. 

Gao, P. (1996) Determination of the composition of delavirdine mesylate polymorph and pseudopolymorph... 

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