Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 1998 Sep;46(3):221-8.
doi: 10.1046/j.1365-2125.1998.00776.x.

Caffeine based measures of CYP1A2 activity correlate with oral clearance of tacrine in patients with Alzheimer's disease

R J Fontana  1 , T M deVries, T F Woolf, M J Knapp, A S Brown, L S Kaminsky, B K Tang, N L Foster, R R Brown, P B Watkins
Affiliations
Clinical Trial

Caffeine based measures of CYP1A2 activity correlate with oral clearance of tacrine in patients with Alzheimer's disease

R J Fontana et al. Br J Clin Pharmacol. 1998 Sep.

Abstract

Aims: To study the potential utility of caffeine based probes of CYP1A2 enzyme activity in predicting the pharmokinetics of tacrine in patients with Alzheimer's disease.

Methods: The pharmokinetics of a single 40 mg oral dose of tacrine were measured in 19 patients with Alzheimer's disease. Each patient also received 2 mg kg(-1) [13C-3-methyl] caffeine orally and had breath and urine samples collected.

Results: Tacrine oral clearance (CL F(-1) kg(-1)), which varied 15-fold among the patients, correlated significantly with the 2 h total production of 13CO2 in breath (r=0.56, P=0.01), and with each of two commonly used urinary caffeine metabolite ratios: the 'paraxanthine/caffeine ratio' (1,7X + 1, 7U)/1,3,7X) (r=0.76, P=0.0002) and the 'caffeine metabolic ratio' (AFMU + 1X + 1U)/1, 7U)(r=0.76, P=0.0001).

Conclusions: These observations support a central role for CYP1A2 in the in vivo disposition of tacrine and the potential for drug interactions when tacrine treated patients receive known inducers or inhibitors of this enzyme. The magnitude of the correlations we observed, however, are probably not sufficient to be clinically useful in individualizing tacrine therapy.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Individual (n=19) plasma tacrine concentrations after oral administration of 40 mg tacrine.
Figure 2
Figure 2
Individual (n=19) oral clearance of tacrine (CLF−1 kg−1) and estimates of CYP1A2 activity. a=Caffeine Breath Test (CBT), b=Caffeine metabolic ratio (CMR), c=Paraxanthine/caffeine urinary metabolite ratio (PCUR), open circle, female; solid circle, male.
Figure 3
Figure 3
Individual subject correlations of tacrine and 1-OH tacrine area under the curve (AUC) values, r=0.892, P=0.0001. open circle, female; solid circle, male.
See this image and copyright information in PMC

References

    1. Farlow M. Management of Alzheimer's Disease: Today's Options and Tomorrow's Opportunities. Alz Dis Assoc Disord. 1994;8(Suppl 2):S50–S57.
    1. Knapp MJ, Knopman DS, Solomon PR, Pendlebury WW, Davis CS, Gracon SI. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. JAMA. 1994;271:985–991. - PubMed
    1. Parke-Davis Pharmaceuticals Warner Lambert. Cognex (tacrine) package insert. Parke Davis Pharm. 1994.
    1. Ford JM, Truman CA, Wilcock GK, Roberts CJ. Serum concentrations of tacrine hydrochloride predict its adverse effects in Alzheimer's disease. Clin Pharmacol Ther. 1993;53:691–695. - PubMed
    1. Hartvig P, Askmark H, Aquilonius SM, Wiklund L, Lindstrom B. Clinical Pharmacokinetics of intravenous and oral 9-amino-1,2,3,4-tetrahydroacridine, Tacrine. Eur J Clin Pharmacol. 1990;38:259–263. - PubMed

Publication types

MeSH terms