Table 2 Associations between caffeine metabolite ratios with clozapine, norclozapine, and olanzapine plasma concentration-to-dose ratios and with clozapine-to-norclozapine ratios.

From: Dietary caffeine to assess CYP1A2 activity, tailor clozapine doses, and predict treatment response: genetic, epigenetic and clinical analyses

 

Clozapine [ng/mL] / dose [mg/d]a

Norclozapine [ng/mL] / dose [mg/d]a

Clozapine [ng/mL] / Norclozapine [ng/mL]a

Olanzapine [ng/mL] / dose [mg/d]a

Predictors

Estimates

95% CI

p-value

Estimates

95% CI

p-value

Estimates

95% CI

p-value

Estimates

95% CI

p-value

(Intercept)

−0.23

−0.97 – 0.52

0.55

−0.57

−1.37 − 0.23

0.16

0.30

−0.26 – 0.86

0.29

0.47

−0.07 – 1.02

0.09

Caffeine metabolic ratiosb

−0.30

−0.40 – −0.20

<0.001

−0.21

−0.31 – −0.11

<0.001

−0.09

−0.16 – −0.02

0.01

−0.04

−0.10 – 0.02

0.21

Age (10 years)

0.08

0.03 – 0.13

0.001

0.09

0.03 – 0.14

0.002

−0.00

−0.04 – 0.03

0.84

0.05

−0.00 – 0.10

0.06

Sex (Female)

0.13

−0.05 – 0.31

0.17

0.11

−0.08 – 0.31

0.25

0.00

−0.14 – 0.14

0.98

0.27

0.10 – 0.44

0.002

Body Mass Index

0.03

0.01 – 0.05

0.003

0.02

−0.00 – 0.04

0.10

0.01

−0.00 – 0.03

0.10

0.02

0.00 – 0.03

0.03

Smoking

−0.24

−0.45 – −0.04

0.02

−0.37

−0.59 – −0.15

0.001

0.16

0.01 – 0.32

0.04

−0.41

−0.57 – −0.25

<0.001

Time (hours)c

−0.04

−0.07 – −0.01

0.008

−0.04

−0.07 – −0.01

0.01

0.00

−0.02 – 0.02

0.88

−0.02

−0.04 – 0.00

0.04

Patients

120

120

120

146

Observations

164

164

164

222

Marginal R2 / Conditional R2

0.399/0.577

0.339/0.616

0.093/0.577

0.247/0.749

Partial R2 for:

 Caffeine metabolic ratios

14.94%

  

7.37%

  

3.17%

  

0.51%

  

 Age

5.36%

  

5.66%

  

0.05%

  

1.74%

  

 Sex

1.65%

  

1.36%

  

0.05%

  

3.67%

  

 Body Mass Index

5.04%

  

1.62%

  

2.21%

  

1.32%

  

 Smoking

2.83%

  

5.68%

  

2.72%

  

9.40%

  

 Time

2.59%

  

2.02%

  

0.00%

  

0.59%

  
  1. aLog transformed to better approximate a normal distribution.
  2. bCalculated by dividing paraxanthine by caffeine plasma levels and multiplying the ratio by 1.07769 (Molecular mass ratio).
  3. cTime spent between last clozapine or olanzapine intake and blood sampling in hours.
  4. Significant p-values in bold. Of note, regression coefficients for log-transformed variables represent proportional changes. Percent change = (e^β−1) × 100. For example: β = −0.30 → (e^−0.30−1) × 100 = −25.9% (a 25.9% decrease).
  5. CI Confidence Interval, d day, mg milligram, ml milliliter, ng nanogram.
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