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Biomedical subjects

C Higham

Publications and source records attributed to C Higham.

9 recordsLinked to original sources
PubMed1998

A phase I/II study of the protease inhibitor ritonavir in children with human immunodeficiency virus infection.

BACKGROUND: Ritonavir, a potent antiretroviral protease inhibitor, has been approved for the treatment of adults and children with human immunodeficiency virus (HIV) infection. In a phase I/II study, we assessed the safety, tolerability, and pharmacokinetic profile of the oral solution of ritonavir in HIV-infected children and studied the preliminary antiviral and clinical effects. METHODS: HIV-infected children between 6 months and 18 years of age were eligible. Four dose levels of ritonavir oral solution (250, 300, 350, and 400 mg/m given every 12 hours) were evaluated in two age groups (</=2 years, >2 years). Ritonavir was administered alone for the first 12 weeks and then in combination with zidovudine and/or didanosine. Clinical and laboratory parameters were monitored every 2 to 4 weeks. RESULTS: A total of 48 children (median age, 7.7 years; range, 0.5 to 14.4 years) were included in this analysis. Dose-related nausea, diarrhea, and abdominal pain were the most common toxicities and resulted in discontinuation of ritonavir in 7 children. Ritonavir was well absorbed at all dose levels, and plasma concentrations reached a peak 2 to 4 hours after a dose. CD4 cells counts increased by a median of 79 cells/mm3 after 4 weeks of monotherapy and were maintained throughout the study. Plasma HIV RNA decreased by 1 to 2 log10 copies/mL within 4 to 8 weeks of ritonavir monotherapy, and this level was sustained in patients enrolled at the highest dose level of 400 mg/m for the 24-week period. CONCLUSIONS: The oral solution of ritonavir has potent antiretroviral activity as a single agent and is relatively well tolerated by children when administered alone or in combination with zidovudine or didanosine.

Administration, Oral↗
PubMed1983

Problems for rheumatic patients in opening dispensed drug containers.

The ability of 50 rheumatoid arthritis patients with hand involvement and 50 normal control subjects to open a range of reclosable tablet containers and unit dose packs was tested. Child-resistant containers, particularly the clic-loc type, proved the most difficult for patients and control subjects to open. Smaller containers were less easy to open than comparable ones of a larger size. Only 54% patients were able to remove a suppository from its wrapping. Blister packs and conventional screw-capped tablet bottles were easiest to open. Dispensing of drugs for rheumatic patients in child-resistant containers should be limited to those without hand involvement.

Activities of Daily Living↗
PubMed1983

Dose-response study with ibuprofen in rheumatoid arthritis: clinical and pharmacokinetic findings.

Clinical response and plasma pharmacokinetics were studied in 20 rheumatoid patients receiving three dosages of ibuprofen. There was a significant response to 1600 mg daily of ibuprofen by all three clinical measurements but increasing the daily dosage to 2400 mg produced no overall increase in response. The AUC increased with increasing daily drug dosages from 800 to 2400 mg daily and the dose normalised AUC fell by 15% over the same dosage range. The fraction of ibuprofen not bound to plasma proteins increased with increasing dosage and may contribute to the fall in the dose normalised AUC. There was a considerably inter-individual variation in the AUC. There was no significant correlation between AUC and clinical response as measured by articular index and there was a weakly significant correlation between AUC and clinical response as measured by a visual analogue pain index. Pharmacokinetic variables probably account for only a small part of the inter-individual variation in response of rheumatoid patients treated with increasing dosages of the non-steroidal, anti-inflammatory drug ibuprofen.

Adult↗
PubMed1981

A chronic dose-ranging study of the pharmacokinetics of phenylbutazone in rheumatoid arthritic patients.

Phenylbutazone in doses of 200, 300 and 400 mg/day was administered chronically to six rheumatoid arthritic patients. At each steady-state the plasma levels of phenylbutazone, oxyphenbutazone and gamma-hydroxyphenylbutazone as well as the extents of binding of phenylbutazone and oxyphenbutazone to plasma proteins were measured. 2 Plasma concentrations of phenylbutazone did not increase proportionally with dose but when corrected for protein binding unbound concentrations of phenylbutazone did show a proportional increase with dose. 3 Plasma concentrations of oxyphenbutazone decreased with an increase in phenylbutazone dose suggesting either that the elimination of oxyphenbutazone is stimulated or its formation inhibited after chronic administration of phenylbutazone. 4 Binding studies with human serum albumin demonstrated the ability of phenylbutazone and oxyphenbutazone to mutually displace one another. Neither saturation of the protein binding sites nor displacement interactions could account for the changes in binding shown by phenylbutazone with increased dose. 5 gamma-hydroxyphenylbutazone concentrations increased proportionally with phenylbutazone dose reaching 68% of the phenylbutazone concentration in one patient. There was a large inter-subject variation in the gamma-hydroxyphenylbutazone concentrations.

Aged↗