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Aim Our aim was to evaluate the effect of ketoconazole on ritonavir and saquinavir plasma and cerebrospinal fluid (CSF) concentrations. Methods Twelve patients who were human immunodeficiency virus–seropositive and who were receiving 400 mg of ritonavir and 400 mg of saquinavir twice daily completed a nonfasted, two-period, two-group, longitudinal pharmacokinetic study. Blood samples were collected over the daytime 12-hour dosing interval of the protease inhibitors at baseline (period 1, day 0) and after 10 days of coadministration of 200 mg (n = 6) or 400 mg (n = 6) of ketoconazole once daily (period 2, day 10). One set of paired CSF and blood samples was collected between 4 and 5 hours after the dose on both days. Results Ketoconazole significantly increased area under the plasma concentration-time curve, plasma concentration at 12 hours after the dose, and half-life of ritonavir by 29% (95% confidence interval (CI), 13%-46%), 62% (95% CI, 37%-92%), and 31% (95% CI, 13%-51%), respectively. Similar increases of 37% (95% CI, 4%-81%), 94% (95% CI, 41%-167%), and 38% (95% CI, 15%-66%), respectively, were observed for these parameters for saquinavir. Ketoconazole significantly elevated ritonavir CSF concentration by 178% (95% CI, 59%-385%), from 2.4 to 6.6 ng/mL, with no change in paired unbound plasma level (26 ng/mL); this led to a commensurate 181% increase (95% CI, 47%-437%) in CSF/plasma unbound ratio. All pharmacokinetic changes were unrelated to ketoconazole dose or plasma exposures. Corresponding changes for saquinavir CSF pharmacokinetics were insignificant (P > .06); saquinavir CSF levels were unmeasurable in 7 patients (

Non-dystrophic myotonia (NDM) is caused by mutations in muscle chloride and sodium channels. Currently, there is no standardized instrument for documenting symptom frequency and severity in NDM.Subjects used an automated, interactive, telephone-based voice response diary (IVR) to record frequency and severity of stiffness, weakness, pain, and tiredness once a week for 8 weeks, after their baseline visits.We describe the IVR and report data on 76 subjects for a total of 385 person-weeks. Overall there were 5.1 calls per subject. Forty-eight subjects called in 5 or more times, and 14 called in 8 times. Stiffness was both the most frequent and severe symptom. Warm-up and handgrip myotonia were associated with higher severity scores for stiffness.IVR is a convenient technology to allow patient reporting of repeated and real-time symptom frequency and severity, and it is presently being used in a trial of mexiletine in NDM.