Theophylline drug concentrations

Adverse reactions to drugs differ in both type and incidence in the pediatric population. Because of immature metabolic pathways, infants and children may have different metabolic patterns than adults. This at least partially explains why neonates require lower theophylline serum concentrations for the treatment of neonatal apnea and why the incidence of hepatotoxi-city following acetaminophen overdose is much lower in young children than in adults [44,45]. Antibiotic adverse effects unique to the pediatric population may... 

The intrinsic dissolution rate method is most useful where the equilibrium method cannot be used. For example, when one wishes to examine the inLuence of crystal habit, solvates and hydrates, polymorphism, and crystal defects on apparent solubility, the intrinsic dissolution rate method will usually avoid the crystal transitions likely to occur in equilibrium methods. However, crystal transitions can still occur at the surface as in the case of anhydrous theophylline (De Smidt, 1986), where the anhydrous form converts to the hydrate and the intrinsic dissolution rate changes over time. In these cases, the application oflaer optical probe, which permits the detection of the drug concentration every few seconds, may prove to be very advantageous. 

For a few drugs such as theophylline, saliva drug concentrations have been employed to supplement the collection of blood samples. However, the intersubject and intrasubject variability in saliva/plasma ratios have generally precluded the sole use of saliva drug concentrations to assess bioavailability. For some drugs such as cephalosporin antibiotics, clinical studies may also include a determination of appearance of drug in other body fluids such as the cerebrospinal fluid and bile. 

Fig. 6 Theophylline serum concentration in an individual subject after a single 1500 mg dose of Theo-24 taken during fasting, period during which this patient experienced nausea, repeated vomiting, or severe throbbing headache. The pattern of drug release during the food regimen is consistent with dose-dumping. (From Ref. l)...

An example of this approach can be obtained by continuing the theophylline patient case from the section on drug dosing in liver disease. In this example, a 55-year-old, 70-kg man with liver cirrhosis was prescribed a loading dose of theophylline 350 mg intravenously over 20 to 30 minutes, followed by a maintenance dose of 15 mg/h of theophylline as a continuous infusion. The infusion began at 9 A.M., blood samples were obtained at 10 A.M. and 4 P.M., and the clinical laboratory reported the theophylline serum concentrations as 10.9 and 12.3 mg/L, respectively. The patient s theophylline clearance and revised continuous infusion to maintain a Css of 15 mg/L can be computed as follows (patient s Vo estimated at 0.5 L/kg) ... 

Theophylline is a pharmaceutical drug that is sometimes used to help with lung function. You observe a case where the initial lab results indicate that the concentration of theophylline in a patient s body decreased from 2.0 x 10 AT to 1.0 x 10 AT in 24 hours. In another 12 hours the drug concentration was found to be 5.0 x 10 AT. What is the value of the rate constant for the metabolism of this drug in the body ... 

FIGURE 10.2 Toxicity related to theophylline serum concentration in 48 patients receiving intravenous aminophylline. (From Hendeles, L. et al., Drug Intell. Clin. Pharm., 11 12-18, 1977. With permission.)... 

Pharmacokinetic Drug-Drug Interactions Resulting in Changes in Theophylline Serum Concentration (percentage values represent average changes)... 

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