Caffeine polymorphs

The importance of adenosine deaminase in the duration and intensity of sleep in humans has been noted recently (Retey et al. 2005). Animal studies suggest that sleep needs are genetically controlled, and this also seems to apply in humans. Probably, a genetic variant of adenosine deaminase, which is associated with the reduced metabolism of adenosine to inosine, specifically enhances deep sleep and slow wave activity during sleep. Thus low activity of the catabolic enzyme for adenosine results in elevated adenosine, and deep sleep. In contrast, insomnia patients could have a distinct polymorphism of more active adenosine deaminase resulting in less adenosine accumulation, insomnia, and a low threshold for anxiety. This could also explain interindividual differences in anxiety symptoms after caffeine intake in healthy volunteers. This could affect the EEG during sleep and wakefulness in a non-state-specific manner. 

Due to the polymorphic acetylation of amonafide, a phenotyping procedure for amonafide acetylation using caffeine as a probe was evaluated in cancer patients. Slow and fast acetylators of both caffeine and amonafide were identified. Fast ace-... 

Sachse C, Brockmoller J, Bauer S, Roots I. Functional significance of a C—>A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 1999 47(4) 445—449. 

The hydrogen bonding scheme is identical in both crystals as seen in Fig. 11 and Fig. 12. The molecules pack so as to provide what maybe aptly described as a hydrogen-bonded comb, with a GA 36 backbone and caffeine 35 teeth. In fact, the major difference between the two polymorphs on the secondary level of supramolecular architecture resides in the torsion of the GA 36 aliphatic chain. 

NIRA provides a non-destructive alternative to differential scanning calorimetry for the determination of polymorphic forms of drugs, e.g. the polymorphic forms of caffeine. NIRA has also been used to determine optical purity. While the pure opposite enantiomers of a substance have identical NIR spectra, mixing two... 

The AHR must dimerize with ARNT in order to bind to AH response elements and alter gene transcription. Several polymorphic sites have been identified in the human ARNT gene but none of these appears to affect CYP1A2 activities in vivo as judged by caffeine phenotyping (102). 

Welfare MR, Aitkin M, Bassendine MF, Daly AK. Detailed modelling of caffeine metabolism and examination of the CYP1A2 gene lack of a polymorphism in CYP1A2 in Caucasians [published erratum appears in Pharmacogenetics 1999 Dec 9(6) 782]. Pharmacogenetics 1999 9 367-375. 

Han XM, Ou-Yang DS, Lu PX et al. (2001) Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G-2964A and C734A polymorphisms of human CYP1A2. Pharmacogenetics 11 429-435... 

Sachse S, Bhambra U, Smith G et al. (2003) Polymorphisms in the cytochrome P4501A2 gene (CYP1A2) in colorectal cancer patients and control allele frequencies, linkage disequilibrium and influence on caffeine metabolism. Br J Clin Pharmacol 55 68-76... 

A typical example of the characterization of a polymorphic system by FT Raman spectroscopy has been given by Gu and Jiang (1995) while an application of the technique with near infrared excitation to the polymorphic cimetidine system has been described by Tudor et al. (1991). The FT Raman technique has been compared to infrared diffuse reflection spectroscopy in the study of the polymorphs of spironolactone (Neville et al. 1992), and the pseudopolymorphic transition of caffeine hydrate (i.e. loss of solvent) has been monitored using the technique (de Matas et al. 1996). 

Polymorphism Crystallinity. One of the earliest reported uses of NIR for polymorphism was for the polymorphs of caffeine in 1985.In 1987, Gimet and Luong used NIR to ascertain changes in crystallinity during processing. 

Manduva R, Keti VL. Banks SR. et al. Calorimetric and spatial characterisation of polymorphic transitions in caffeine using quasi-isothermal MTDSC and localised thermo-mechanical analysis. J Wiarm Sci 2007 97(2008) 1285-1300,... 

Lehto VP. Laine E. A kinetic study of polymorphic transition of anhydrous caffeine with mtcrocalorimctcr. Thermochim Acta 1988 317 47-58. 

Although not a polymorphic phase in the formal sense, the amorphous state can represent an important quantity of measure in a crystalline sample. A general XRPD procedure for such work has been described,31 and similar approaches have been reported for cilastatin sodium,32 caffeine,33 imipenem,34 acetaminophen,35 and a Lumaxis analog.36... 

CYP1A2 Antidepressants amitriptyline, clomipramine, imipramine, fluvoxamine Neuroleptics haloperidol, phenothiazines, thiothixene, clozapine, olanzapine Others tacrine, caffeine, theophylline, acetaminophen, phenacetin No report of polymorphism until 1999 significance of following findings remains unclear 1C reduced activity 23% in Japanese 1F higher inducibility 32% in Caucasians... 

Acetylation of drugs is also associated with genetically determined interindividual and interethnic differences. Differences in isoniazid toxicity between Asians and Caucasians are due to acetylation enzyme polymorphism. The majority (78%-93%) of Chinese and East Asians are fast acetylators, whereas only 50% of whites and African Americans are fast acetylators (Weber 1987). This is clinically important, because several psychoactive compounds (e.g., caffeine, clonazepam, nitrazepam, and phenelzine) are metabolized through acetylation (Sjoqvist et al. 1997). 

In 1985, Ciurczak [40] reported using NIR to distinguish between the polymorphic forms of caffeine. This technique has been applied to proprietary drug substances, but data are unavailable for public presentation. 

Oxidative metabolism of clozapine was found to correlate with caffeine metabolism (462)and is thus largely carried out by cytochrome P4501A2 (CYP1A2). No correlation with CYP2D6 polymorphism was found (461, 462). Several interaction studies of clozapine with SSRI antidepressants have been reported (465-469). Fluvoxamine increased plasma concentrations of clozapine in schizophrenic patients (463,464), presumably through inhibition of CYP1A2 catalyzed N-demethylation (465). Fluoxetine was found to increase the plasma concentrations of clozapine and its major metabolites, suggesting that this SSRI must interfere with pathways other than N-demethylation and N-dealkylation (466). Two other SSRIs, paroxetine (463) and citalopram (467), had no apparent effects on clozapine levels. 

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