Oral Baclofen Pharmacokinetics and Pharmacodynamics in Children With Spasticity

Exclusion Criteria

• •1. Hypersensitivity to baclofen.
• •2. Selective dorsal rhizotomy.
• •3. Active intrathecal baclofen pump within the past 6 months.
• •4. Use of botulinum toxin in past 4 months or use any time during the study.
• •5. Use of tone altering medications (e.g. baclofen, benzodiazepines, levodopa, trihexyphenidyl) for \>3 consecutive days duration within the past 4 months.
• •6. Start of any drug or product known to be a significant cytochrome P450 enzyme inducer or inhibitor within the past 30 days.
• •7. Orthopaedic surgery within the past year or any time during the study.
• •8. Abdominal surgery within the past six months or any time during the study.
• •9. Uncontrolled seizures (baseline seizure frequency \>1 per month or history of more than 2 prolonged seizures lasting longer than 5 minutes duration within the past year.
• •10. Severe behavior difficulties or psychiatric disturbance
• •11. Proven gastric dysmotility: known history of abnormal gastric emptying study and/or history of vomiting 3 or more times per week.
• •12. Severe Gastroesophageal Reflux Disease: known history of esophagitis (documented on abnormal endoscopy or biopsy).
• •13. Malnutrition: defined as triceps skin fold thickness less than 5th or greater than 95th percentile for age.
• •14. Renal or Liver disease: Elevated bilirubin, LFTs greater than twice the upper limit of normal, reduced BUN/Cr ratio (\<5), or abnormal creatinine clearance that is clinically significant as determined by the investigator.
• •15. Abnormal CBC: Anemia, polycythemia, neutropenia, leukocytosis, thrombocytopenia, or thrombocytosis clinically significant as determined by the investigator.
• •16. Pregnancy or lactation.
• •17. Severe respiratory or cardiac disease: Requirement for prolonged supplemental oxygen (\>7 days), history of clinically significant congenital heart disease, congestive heart failure or cardiomegaly, and/or hospital admission within past 6 months for cardiac symptoms or respiratory distress.
• •18. Previous baclofen failure: Lack of response to baclofen or presence of unacceptable side effects. If previous baclofen therapy was tried \>4 months prior to study and discontinued, the decision to enroll subject will be at the discretion of the site investigator and reason for discontinuation of oral baclofen will be recorded.
• •19. Use of medications that interfere with measurements of serum creatinine levels within the past 14 days (e.g., trimethoprim-sulfa, fibric acid derivatives other than gemfibrizol, keto acids, salicylates, some cephalosporins, cimetidine, phenacemide) .
• •20. Subject tests positive at screening for the hepatitis B surface antigen or hepatitis C antibody, or has a history of a positive result for one of these tests.
• •21. Subject is known to have tested seropositive for the human immunodeficiency virus (HIV) or subject is concomitantly receiving anti-retroviral therapy.
• •22. Any serious, unstable medical illness or clinically significant abnormal laboratory assessment that would adversely impact the scientific interpretability or unduly increase the risks of the protocol.
• •23. Subject has a disorder or history of a condition, other than that related to CP that could interfere with drug absorption, distribution, metabolism, or excretion.
• •24. Any condition which would make the patient