Caffeine clearance range/distribution and what determines it

Question

A Sci. Am. article mentioned that

Some people's bodies clear caffeine within a few hours, but lunchtime coffee may still be in the system of other people even late at night.

Although they have some links in there, it looks like none talk of this topic specifically... So is there some data on how wide of a range of clearance of caffeine has been encountered, or other distributional parameters related to this? Is caffeine clearance speed for instance genetically determined in some known way?

Answer 1

There are many parameters to consider. The caffeine clearance is influenced by genetics, environmental factors, age, drug interactions, pregnancy, illnesses, day and time of day, habituation, what species you look at, etc.

We do not have a complete picture in terms of perfect predictability. But we have quite a few individual lines of cause and effect cleared up to a certain degree.

Caffeine is absorbed in the intestine quite rapidly and almost completely. Then generally 97% are metabolised into 'something' and only 3% excreted as is, on average. Caffeine concentration is characterised in half life.

Drinking grapefruit for example before drinking coffee increases that half life, as the fruit contains quite significant levels of naringenin, bergamottin and hydroxybergamottin. These substances have in common that they inhibit cytochrome p450 in the liver (effecting quite a few drugs by the way). This effect was only found out in 1989 by chance.

Calculating all the variables will not be possible in this answer. Let's focus on genetics of caffeine pharmacokinetcis in humans.

Jakob Strube: "Studie zu erblichen Einflüssen auf die Pharmakokinetik von Midazolam und Koffein. (Study for the evaluation of heritability of midazolam and caffeine pharmacokinetics)", Dissertation, Georg-August-Universität Göttingen, 2015. (PDF)

This small study found an unexpectedly marked hereditary component in caffeine clearance and also gave a range from own measurements and compared those with previous literature:

Clearance/F* [ml/min]              40 - 431    own measurement
Clearance/F·KG-1* [ml/min·kg- 1]   0,35 – 5,08 own measurement

                                   1,12±0,3    Newton et al. 1981
                                   2,20±1,02   Lelo et al 1986 a
                                   2,07±0,96   Lelo et al 1986 b
                                   2,2±1,67    Kamimori et al. 2002
                                   1,58±0,54   Perera et al 2011
t1/2 [Minuten]                     97,6 - 735  own measurement

                             meist 246 - 342; bis zu 600 Lindopharm GmbH 2004
                                   
                                   162 - 744   Newton et al. 1981
                                   246±78      Lelo et al. 1986 b
                                   240 - 300   Kot und Daniel 2008
                                   330±114     Perera et al. 2011
Cmax [μg/l]                        668 - 1984  eigene Messung
                                   1170±980    Kamimori et al. 2002
                                   750±250     (normiert auf 50 mg-Dosis) Perera et al. 2011
Tmax [Minuten]                     26 - 200    eigene Messung
                                   30 - 40     Lindopharm GmbH 2004
                                   30 - 90     Newton et al. 1981
                                   60          Perera et al. 2011
                                   85,2±54     Kamimori et al. 2002

V/F [l]                            22,9 - 68,7 eigene Messung
V/F·KG [l/kg]                      0,38 - 0,81 eigene Messung
                                   0,52 - 1,06 Lindopharm GmbH 2004
                                   0,5 - 0,75 Kot und Daniel 2008
                                   0,781±0,208 Kamimori et al. 2002