The Effect of Age, Gender, and Sexual Maturation on the Caffeine Breath Test

Lambert, George H.; Schoeller, Dale A.; Kotake, Alvin N.; Flores, Carlos; Hay, Deborah

doi:10.1159/000457262

Cited by 93 publications

(58 citation statements)

References 22 publications

(52 reference statements)

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“…Our results could therefore indicate that adolescence could be characterized by pharmacokinetic specificities compared to the pharmacokinetics in both younger children and adults, so that the current pharmacokinetic assumption that places adults and adolescents in the same category should be reconsidered, at least for metabolized drugs. This was previously suggested for CYP 1A2, as the rate of demethylation of caffeine decreased in early puberty for girls and late puberty for boys (20). However, it must be noticed that similar sex-related differences in the pharmacokinetics of indinavir (10) and saquinavir (25), two other PIs metabolized by CYP 3A4, have been reported in adults.…”

Section: Fig 3 Goodness Of Fit Visualized On the Weighted Residualssupporting

confidence: 55%

Population Analysis of Weight-, Age-, and Sex-Related Differences in the Pharmacokinetics of Lopinavir in Children from Birth to 18 Years

Jullien

Urien

Hirt

et al. 2006

Antimicrob Agents Chemother

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The pharmacokinetics of lopinavir were investigated by the use of a population approach performed with the nonlinear mixed effect modeling program NONMEM and 157 children ranging in age from 3 days to 18 years. The pharmacokinetics of lopinavir were well described by a one-compartment model in which the absorption and the elimination rate constants were equal. Typical population estimates of the apparent volume of distribution (V/F) and plasma clearance (CL/F) were 24.6 liters and 2.58 liters/h, respectively. The lopinavir V/F and CL/F were both related to body weight (BW), with an important increase in weight-normalized CL/F for the lowest BW. Combined treatment with lopinavir and nevirapine was found to increase the CL/F. The lopinavir CL/F was also age and sex related, as a 39% increase was observed after the age of 12 years for boys compared to the CL/F for girls. The consequences of these pharmacokinetic discrepancies and the necessity to modify the currently recommended dosage regimen should be further investigated.Lopinavir is a protease inhibitor (PI) used for the treatment of human immunodeficiency virus (HIV) infection in children and adults. Lopinavir can be administered to children older than 6 months of age by the use of a liquid formulation as well as by the use of a solid oral formulation, both of which contain ritonavir for pharmacokinetic enhancement, at recommended lopinavir/ritonavir doses of 12/3 mg/kg of body weight (BW) twice daily (BID) for children with BWs between 7 and 14 kg and 10/2.5 mg/kg BID for children with BWs between 15 and 40 kg. For children with body weights greater than 40 kg, the 400/100-mg BID adult dosage regimen is recommended. Children younger than 6 months of age were not investigated in previously published studies (3,27). This lack of data can explain to some extent why lopinavir is not recommended for use in children younger than age 6 months. Nevertheless, there are clinical situations, such as the presence of a viral strain less sensitive to the other antiretrovirals, which could require the administration of lopinavir to very young children. Another pediatric population for which pharmacokinetic data are lacking is children with BWs greater than 40 kg. However, this lack of data for adolescents is a very common phenomenon and is relevant not only to lopinavir. Frequently, adolescents are considered similar to adults from a pharmacokinetic point of view, which explains why adolescents often receive the recommended adult dosage regimen. However, adolescence is characterized by physiological and hormonal changes (26, 30), the possible consequences of which on the pharmacokinetics and metabolism of drugs are still unknown. Because pharmacokinetic data for children younger than age 6 months and adolescents are lacking, the relationships between lopinavir pharmacokinetic parameters and the individual characteristics of children are also not known. These relationships are nevertheless important for optimization of the lopinavir dosage regimen, as several studies perform...

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Section: Fig 3 Goodness Of Fit Visualized On the Weighted Residualssupporting

confidence: 55%

Population Analysis of Weight-, Age-, and Sex-Related Differences in the Pharmacokinetics of Lopinavir in Children from Birth to 18 Years

Jullien

Urien

Hirt

et al. 2006

Antimicrob Agents Chemother

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“…Multivariate analysis confirmed that the only independent predictors of the CBT were smoking status and disease state. This is in accord with previous studies showing that caffeine metabolism does not appear to be influenced by age beyond adolescence 29,30 and sex. 30,31 It generally has been accepted that the 2-hour cumulative exhalation of labeled CO 2 represents the best parameter of caffeine clearance in the adult.…”

Section: Discussionsupporting

confidence: 93%

Validity of the 13C-caffeine breath test as a noninvasive, quantitative test of liver function

Park

2003

Hepatology

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The properties of caffeine render it an ideal substrate for a quantitative test of liver function. The aim of this study was to determine whether the caffeine breath test (CBT) using orally administered 13 C-caffeine correlates reliably with plasma caffeine clearance and reflects varying degrees of liver dysfunction. The CBT was performed in 25 healthy controls; 20 subjects with noncirrhotic, chronic hepatitis B or C; and 20 subjects with cirrhosis. Plasma caffeine clearance was assayed simultaneously with the CBT in a cohort of these subjects. Over a broad range of caffeine clearances, the CBT exhibited a highly significant correlation with plasma clearance (r ‫؍‬ 0.85, P < .001). Cirrhotic patients were characterized by significantly reduced CBT values (1.15 ؎ 0.75 ‚‰ mg ؊1 ) compared with controls (2.23 ؎ 0.76; P ‫؍‬ .001) and hepatitic patients (1.83 ؎ 1.05; P ‫؍‬ .04). There was a significant inverse relationship between the CBT and Child-Pugh score (r ‫؍‬ ؊.74, P ‫؍‬ .002). The intraclass correlation coefficient between repeated CBTs in 20 subjects with normal and cirrhotic livers was 0.89. Although smoking was associated with an 86% to 141% increase in CBT in all groups, the CBT was able to distinguish control, hepatitic, and cirrhotic smokers (5.36 ؎ 0.82, 3.63 ؎ 1.21, and 2.14 ؎ 1.14, respectively, P ‫؍‬ .001). Multivariate analysis revealed that only smoking (P < .001) and disease state (P ‫؍‬ .001) were significant predictors of the CBT. In conclusion, the 13 C-CBT represents a valid indicator of plasma caffeine clearance and correlates reproducibly with hepatic dysfunction. (HEPATOLOGY 2003;38:1227-1236

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“…The CBT values for the 51 PBB-exposed Michigan subjects (with and without detectable PBB serum levels) and our previously reported adult urban control groups of 28 healthy Illinois nonsmokers and 16 smokers (20,24), all of whom had not been exposed to PBBs, are shown in Figure 2. The PBB-exposed subjects had higher CBT values as compared to the urban nonsmokers (p = 0.02), but had CBT values not different from the urban smokers.…”

Section: Caffeine Breath ¶Istmentioning

confidence: 86%

“…The CBT and CMR may be valuable tools in biochemical epidemiology since both are safe, noninvasive, and can be readily performed in the field in subjects of all ages (24). A good correlation (r2 = 0.54, p = 0.001) was observed between the CBT and CMR, and each test has its unique advantage and disadvantages (28).…”

Section: Discussionmentioning

confidence: 99%

The Caffeine Breath Test and Caffeine Urinary Metabolite Ratios in the Michigan Cohort Exposed to Polybrominated Biphenyls: A Preliminary Study

Lambert¹,

Schoeller²,

Humphrey³

et al. 1990

Environmental Health Perspectives

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A field biochemical epidemiology study was conducted using the Michigan cohort consisting of 51 rural residents exposed to polybrominated biphenyls (PBB). The study had three major objectives: a) to determine the serum half-life of the major PBB congener, hexabromobiphenyl (HBB), in the human, b) to determine if the PBB-exposed subjects had elevated cytochrome P4501 function as determined by the caffeine breath test (CBT) and the caffeine urinary metabolite ratio (CMR), and c) to determine the applicability of the CBT and CMR in field studies. PBB serum levels were detected in 36 of the 51 PBB-exposed subjects. The serum half-life of HBB was determined by comparing the current serum HBB values to the subject's previous serum values obtained 5 to 8 years earlier. The median HBB half-life was 12 years (range 4-97 years). The CBT and CMR were elevated in the subjects exposed to PBBs as compared to the values obtained from urban nonsmokers and were similar to those found in adults who smoke. A gender effect was seen in the PBB-exposed subjects, the median CBT and CMR values of the females being lower than the values of males. There was a correlation between the CBT and the HBB serum values (r2=0.2, p=0.01) but not between CMR and HBB serum values. The CBT and CMR were easily conducted in the field and appear to be useful metabolic probes of cytochrome P-4501 activity in human environmental toxicology.

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The Effect of Age, Gender, and Sexual Maturation on the Caffeine Breath Test

Cited by 93 publications

References 22 publications

Population Analysis of Weight-, Age-, and Sex-Related Differences in the Pharmacokinetics of Lopinavir in Children from Birth to 18 Years

Population Analysis of Weight-, Age-, and Sex-Related Differences in the Pharmacokinetics of Lopinavir in Children from Birth to 18 Years

Validity of the 13C-caffeine breath test as a noninvasive, quantitative test of liver function

The Caffeine Breath Test and Caffeine Urinary Metabolite Ratios in the Michigan Cohort Exposed to Polybrominated Biphenyls: A Preliminary Study

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