Development of a urinary metabolic ratio that reflects systemic theophylline elimination during pregnancy

• Main Author: Fritz, Kathleen Gary
• Format: Others
• Published: Scholarly Commons 1993
• Subjects: Asthma in pregnancy; Pregnancy Complications; Medicine and Health Sciences
• Online Access: https://scholarlycommons.pacific.edu/uop_etds/2245; https://scholarlycommons.pacific.edu/cgi/viewcontent.cgi?article=3244&context=uop_etds

A number of studies have investigated the natural history of asthma in pregnancy. Most of the data suggests that the course of asthma for a given patient is unpredictable. Turner, et al.7 summarize the data from all of the English-language literature of studies on the effect of pregnancy on astha. Of 1054 cases examined, 49% of the asthma conditions remained unchanged, 22% got worst and 29% became better.7 Theophylline has been used safely during pregnancy. A review of the literature by O'Brien, showed that no teratogenic effects were associated with the use of theophylline in 117 cases and aminophylline in 76 cases examined.39,40 Blood concentration in newborns have been found to be similar to concentrations in the mothers.41,42,43 Problems developed because theophylline clearance may be altered during pregnancy and necessitate dosage adjustments and careful drug level monitoring.44 RATIONALE FOR STUDY Campbell, et al.45 developed a caffeine urinary metabolic ratio, in which they were able to demonstrate a correlation between changes in metabolic rations and clearance. The change in the metabolic ration explained the alteration in clearance and determined the specific Cytochrome P-450 system involved. Various physiologic changes occurring during pregnancy can cause changes in drug disposition. Pharmacokinetic parameters that need to be considered are plasma protein binding capacity, absorption, drug metabolizing enzyme activity, renal excretory function and volume of distribution.44,46,47 This study was developed to determine if changes in theophylline disposition during pregnancy were due to changes in drug metabolizing enzyme activity. A urinary test was designed to investigate the ratios of unchanged theophylline and theophylline metabolites to monitor changes in the various Cytochrome P-450 isoenzyme systems. Changes in the ratios could provide a noninvasive procedure to assess the effect of modulating agents or conditions (such as pregnancy) on theophylline metabolizing enzyme activity.