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Published in: Obesity Surgery 12/2017

01-12-2017 | Original Contributions

Pharmacokinetics in Morbid Obesity: Influence of Two Bariatric Surgery Techniques on Paracetamol and Caffeine Metabolism

Authors: Albert Goday Arno, Magí Farré, Jose Rodríguez-Morató, Jose M. Ramon, Clara Pérez-Mañá, Esther Papaseit, Ester Civit, Klaus Langohr, Marcel lí Carbó, David Benaiges Boix, Olga Castañer Nino, Juana Antonia Flores Le Roux, Manuel Pera, Luis Grande, Rafael de la Torre

Published in: Obesity Surgery | Issue 12/2017

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Abstract

Purpose

The purpose of the study was to study the impact of the two most common bariatric surgery techniques on paracetamol pharmacokinetics (a marker of gastric emptying) and caffeine metabolism (a marker of liver function).

Materials and Methods

In the present prospective study, we studied 24 morbid obese patients before, at 4 weeks, and 6 months after having undergone sleeve gastrectomy (n = 10) or Roux-en-Y gastric bypass (n = 14). For comparative purposes, 28 healthy controls (14 normal weights and 14 overweights) were also included in the study.

Results

Paracetamol pharmacokinetics was altered in the obese participants leading to lower bioavailability. Bariatric surgery resulted in faster absorption and normalized pharmacokinetic parameters, prompting an increase in paracetamol bioavailability. No differences were found between surgical procedures. In the case of caffeine, the ratio paraxanthine/caffeine did not differ between morbid obese and healthy individuals. This ratio remained unmodified after surgery, indicating that the liver function (assessed by cytochrome P450 1A2 activity) was unaffected by obesity or bariatric surgery.

Conclusions

Paracetamol pharmacokinetics and caffeine plasma levels are altered in severely obese patients. The two studied bariatric surgical techniques normalize paracetamol oral bioavailability without impairing the liver function (measured by cytochrome P450 1A2 activity).
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Literature
1.
go back to reference Stein J, Stier C, Raab H, et al. Review article: the nutritional and pharmacological consequences of obesity surgery. Aliment Pharmacol Ther. 2014;40(6):582–609.CrossRefPubMed Stein J, Stier C, Raab H, et al. Review article: the nutritional and pharmacological consequences of obesity surgery. Aliment Pharmacol Ther. 2014;40(6):582–609.CrossRefPubMed
2.
go back to reference Greenblatt HK, Greenblatt DJ. Altered drug disposition following bariatric surgery: a research challenge. Clin Pharmacokinet. 2015;54(6):573–9.CrossRefPubMed Greenblatt HK, Greenblatt DJ. Altered drug disposition following bariatric surgery: a research challenge. Clin Pharmacokinet. 2015;54(6):573–9.CrossRefPubMed
3.
go back to reference Padwal R, Brocks D, Sharma AM. A systematic review of drug absorption following bariatric surgery and its theoretical implications. Obes Rev. 2010;11(1):41–50.CrossRefPubMed Padwal R, Brocks D, Sharma AM. A systematic review of drug absorption following bariatric surgery and its theoretical implications. Obes Rev. 2010;11(1):41–50.CrossRefPubMed
4.
go back to reference Prescott LF. Kinetics and metabolism of paracetamol and phenacetin. Brit J Clin Pharmacol. 1980;10(S2):291S–8S.CrossRef Prescott LF. Kinetics and metabolism of paracetamol and phenacetin. Brit J Clin Pharmacol. 1980;10(S2):291S–8S.CrossRef
5.
go back to reference Raffa RB, Pergolizzi JV, Taylor R, et al. Acetaminophen (paracetamol) oral absorption and clinical influences. Pain Practice. 2014;14(7):668–77.CrossRefPubMed Raffa RB, Pergolizzi JV, Taylor R, et al. Acetaminophen (paracetamol) oral absorption and clinical influences. Pain Practice. 2014;14(7):668–77.CrossRefPubMed
6.
go back to reference Heading RC, Nimmo J, Prescott LF, et al. The dependence of paracetamol absorption on the rate of gastric emptying. Br J Pharmacol. 1973;47(2):415–21.CrossRefPubMedPubMedCentral Heading RC, Nimmo J, Prescott LF, et al. The dependence of paracetamol absorption on the rate of gastric emptying. Br J Pharmacol. 1973;47(2):415–21.CrossRefPubMedPubMedCentral
7.
go back to reference Bartholomé R, Salden B, Vrolijk MF, et al. Paracetamol as a post prandial marker for gastric emptying, a food-drug interaction on absorption. PLoS One. 2015;10(9):e0136618.CrossRefPubMedPubMedCentral Bartholomé R, Salden B, Vrolijk MF, et al. Paracetamol as a post prandial marker for gastric emptying, a food-drug interaction on absorption. PLoS One. 2015;10(9):e0136618.CrossRefPubMedPubMedCentral
8.
go back to reference Renner E, Wietholtz H, Huguenin P, et al. Caffeine: a model compound for measuring liver function. Hepatology. 1984;4(1):38–46.CrossRefPubMed Renner E, Wietholtz H, Huguenin P, et al. Caffeine: a model compound for measuring liver function. Hepatology. 1984;4(1):38–46.CrossRefPubMed
9.
go back to reference Carrillo JA, Christensen M, Ramos SI, et al. Evaluation of caffeine as an in vivo probe for CYP1A2 using measurements in plasma, saliva, and urine. Ther Drug Monit. 2000;22(4):409–17.CrossRefPubMed Carrillo JA, Christensen M, Ramos SI, et al. Evaluation of caffeine as an in vivo probe for CYP1A2 using measurements in plasma, saliva, and urine. Ther Drug Monit. 2000;22(4):409–17.CrossRefPubMed
10.
go back to reference Doude van Troostwijk LJ, Koopmans RP, Guchelaar H-J. Two novel methods for the determination of CYP1A2 activity using the paraxanthine/caffeine ratio. Fundam Clin Pharmacol. 2003;17(3):355–62. Doude van Troostwijk LJ, Koopmans RP, Guchelaar H-J. Two novel methods for the determination of CYP1A2 activity using the paraxanthine/caffeine ratio. Fundam Clin Pharmacol. 2003;17(3):355–62.
11.
go back to reference Hubbard V, Hall H. Gastrointestinal surgery for severe obesity. Obes Surg. 1991;1(3):257–65. Hubbard V, Hall H. Gastrointestinal surgery for severe obesity. Obes Surg. 1991;1(3):257–65.
12.
go back to reference Benaiges D, Goday A, Pedro-Botet J, et al. Bariatric surgery: to whom and when? Minerva Endocrinol. 2015;40(2):119–28.PubMed Benaiges D, Goday A, Pedro-Botet J, et al. Bariatric surgery: to whom and when? Minerva Endocrinol. 2015;40(2):119–28.PubMed
13.
go back to reference Vidal P, Ramón JM, Goday A, et al. Laparoscopic gastric bypass versus laparoscopic sleeve gastrectomy as a definitive surgical procedure for morbid obesity. Mid-Term Results Obes Surg. 2013;23(3):292–9.CrossRefPubMed Vidal P, Ramón JM, Goday A, et al. Laparoscopic gastric bypass versus laparoscopic sleeve gastrectomy as a definitive surgical procedure for morbid obesity. Mid-Term Results Obes Surg. 2013;23(3):292–9.CrossRefPubMed
14.
go back to reference Christensen M, Andersson K, Dalén P, et al. The karolinska cocktail for phenotyping of five human cytochrome P450 enzymes. Clin Pharmacol Ther. 2003;73(6):517–28.CrossRefPubMed Christensen M, Andersson K, Dalén P, et al. The karolinska cocktail for phenotyping of five human cytochrome P450 enzymes. Clin Pharmacol Ther. 2003;73(6):517–28.CrossRefPubMed
15.
go back to reference Hu OY-P, Tang H-S, Lane H-Y, et al. Novel single-point plasma or saliva dextromethorphan method for determining CYP2D6 activity. J Pharmacol Exp Ther. 1998;285(3):955–60.PubMed Hu OY-P, Tang H-S, Lane H-Y, et al. Novel single-point plasma or saliva dextromethorphan method for determining CYP2D6 activity. J Pharmacol Exp Ther. 1998;285(3):955–60.PubMed
16.
go back to reference Carbó M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther. 1989;45(3):234–40.CrossRefPubMed Carbó M, Segura J, De la Torre R, et al. Effect of quinolones on caffeine disposition. Clin Pharmacol Ther. 1989;45(3):234–40.CrossRefPubMed
17.
go back to reference Farré M, Roset P, Pascual J, et al. Estudio de la biodisponibilidad comparativa de la asociación de paracetamol y codeína (Gelocatil Codeína) frente a un preparado de referencia. Dolor. 1999;14:163–71. Farré M, Roset P, Pascual J, et al. Estudio de la biodisponibilidad comparativa de la asociación de paracetamol y codeína (Gelocatil Codeína) frente a un preparado de referencia. Dolor. 1999;14:163–71.
18.
go back to reference Abernethy DR, Divoll M, Greenblatt DJ, et al. Obesity, sex, and acetaminophen disposition. Clin Pharmacol Ther. 1982;31(6):783–90.CrossRefPubMed Abernethy DR, Divoll M, Greenblatt DJ, et al. Obesity, sex, and acetaminophen disposition. Clin Pharmacol Ther. 1982;31(6):783–90.CrossRefPubMed
19.
go back to reference Cappelletti S, Daria P, Sani G, et al. Caffeine: cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol. 2015;13(1):71–88.CrossRefPubMedPubMedCentral Cappelletti S, Daria P, Sani G, et al. Caffeine: cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol. 2015;13(1):71–88.CrossRefPubMedPubMedCentral
20.
go back to reference De Baerdemaeker LE, Mortier EP, Struys MM. Pharmacokinetics in obese patients. Contin Educ Anaesth Crit Care Pain. 2004;4(5):152–5.CrossRef De Baerdemaeker LE, Mortier EP, Struys MM. Pharmacokinetics in obese patients. Contin Educ Anaesth Crit Care Pain. 2004;4(5):152–5.CrossRef
21.
go back to reference Portolés A, Puerro M, Terleira A, et al. A new high-absorption-rate paracetamol 500-mg formulation: a comparative bioavailability study in healthy volunteers. Curr Ther Res. 2003;64(7):401–11.CrossRefPubMedPubMedCentral Portolés A, Puerro M, Terleira A, et al. A new high-absorption-rate paracetamol 500-mg formulation: a comparative bioavailability study in healthy volunteers. Curr Ther Res. 2003;64(7):401–11.CrossRefPubMedPubMedCentral
24.
go back to reference Courcoulas AP, Christian NJ, Belle SH, et al. Weight change and Health outcomes at three years after bariatric surgery among patients with severe obesity. JAMA. 2013;310(22):2416–25.PubMedPubMedCentral Courcoulas AP, Christian NJ, Belle SH, et al. Weight change and Health outcomes at three years after bariatric surgery among patients with severe obesity. JAMA. 2013;310(22):2416–25.PubMedPubMedCentral
25.
go back to reference Kushner RF, Sorensen KW. Prevention of weight regain following bariatric surgery. Curr Obes Rep. 2015;4(2):198–206.CrossRefPubMed Kushner RF, Sorensen KW. Prevention of weight regain following bariatric surgery. Curr Obes Rep. 2015;4(2):198–206.CrossRefPubMed
Metadata
Title
Pharmacokinetics in Morbid Obesity: Influence of Two Bariatric Surgery Techniques on Paracetamol and Caffeine Metabolism
Authors
Albert Goday Arno
Magí Farré
Jose Rodríguez-Morató
Jose M. Ramon
Clara Pérez-Mañá
Esther Papaseit
Ester Civit
Klaus Langohr
Marcel lí Carbó
David Benaiges Boix
Olga Castañer Nino
Juana Antonia Flores Le Roux
Manuel Pera
Luis Grande
Rafael de la Torre
Publication date
01-12-2017
Publisher
Springer US
Published in
Obesity Surgery / Issue 12/2017
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI
https://doi.org/10.1007/s11695-017-2745-z

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