Biomedical subjects

Arno Nolting

Publications and source records attributed to Arno Nolting.

5 recordsLinked to original sources

PubMed2006

Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo-controlled study.

INTRODUCTION: This randomized, double-blind, placebo-controlled, ascending-dose study was conducted in healthy volunteers to evaluate the safety of the investigational cyanide antidote hydroxocobalamin. METHODS: Four ascending dosing groups received intravenous doses of 2.5, 5, 7.5 or 10 g hydroxocobalamin over 7.5 to 30 minutes at a constant infusion rate. Volunteers (n = 136) randomized 3:1 to receive hydroxocobalamin or placebo underwent a 4-day in-house observation after infusion on Day 1 and follow-up visits on Days 8, 15, and 28. RESULTS: The most common drug-related adverse events were asymptomatic and self-limiting chromaturia and reddening of the skin, which are attributed to the red color of hydroxocobalamin. Other adverse events included pustular/papular rash, headache, erythema at the injection site, decrease in lymphocyte percentage, nausea, pruritus, chest discomfort, and dysphagia. Hydroxocobalamin was associated with an increase in blood pressure in some volunteers. Blood pressure changes peaked toward the end of hydroxocobalamin infusion and typically returned to baseline levels by 4 hours postinfusion. Maximum mean changes from baseline in systolic blood pressure ranged from 22.6 to 27.0 mmHg across hydroxocobalamin doses compared with 0.2 to 6.7 mmHg in the corresponding placebo groups. Maximum mean change from baseline in diastolic blood pressure ranged from 14.3 to 25.4 mmHg across hydroxocobalamin doses compared with -3.0 to 3.8 mmHg in the corresponding placebo groups. Two allergic reactions that occurred within minutes after start of the 5- and 10-g hydroxocobalamin infusions were successfully managed with dexamethasone and/or dimethindene maleate. CONCLUSION: Timely intervention for acute cyanide poisoning could entail administration of an antidote in the prehospital setting based on a presumptive diagnosis. Results of this placebo-controlled study in healthy volunteers corroborate previous studies and French postmarketing experience in cyanide-exposed patients in suggesting that the safety profile of hydroxocobalamin is consistent with prehospital or hospital use.

Adolescent↗

PubMed2005

Pharmacokinetic profile of cetuximab (Erbitux) alone and in combination with irinotecan in patients with advanced EGFR-positive adenocarcinoma.

This trial assessed pharmacokinetic interactions between cetuximab and irinotecan. Patients were placed in either in group A (irinotecan 350 mg/m2/3 weeks and 400 mg/m2 cetuximab at week 2 then 250 mg/m2/week) or group B (cetuximab weekly starting week 1 then irinotecan starting week 4). Patient plasma or serum samples from each treatment arm were analysed using HPLC and ELISA. Among 14 patients, compartmental model showed no significant differences in mean plasma AUC at week 1 versus week 4 for irinotecan (44,388 versus 39,800 microg/ml/h) and cetuximab (20,441 versus 23,363 microg/ml/h), respectively. Half-lifes (standard deviations) for irinotecan were 16.02 (+/-8.41) h at week 1 and 13.99 (+/-2.14) h at week 4, and for cetuximab 106 (+/-32) at week 3 and 111 (+/-30) h at week 4. Mean concentration-versus-time profiles either alone or in combination were superimposable for cetuximab and irinotecan. From this study, we conclude that there is no evidence of pharmacokinetic interaction between irinotecan and cetuximab.

Adenocarcinoma↗

PubMed2004

Pharmacokinetic properties of combination oxycodone plus racemic ibuprofen: two randomized, open-label, crossover studies in healthy adult volunteers.

BACKGROUND: As part of ongoing studies to evaluate the analgesic efficacy and pharmacokinetic properties of combination oxycodone plus ibuprofen in the treatment of moderate to severe acute pain, 2 pharmacokinetic studies were conducted. OBJECTIVES: The goals of these studies were to compare the pharmacokinetic properties of monotherapy with oxycodone or ibuprofen with those of a tablet formulation of these 2 agents combined (study A), and to determine whether the absorption of the individual agents when given in the combination tablet was affected by the concomitant ingestion of food (study B). METHODS: Study A was a single-center, open-label, randomized, single-dose, 3-period, 3-way, crossover study. Healthy male subjects received oxycodone 5 mg, ibuprofen 400 mg, or a combination tablet containing both, after an overnight fast of > or =8 hours, on study days 1, 8, and 15. Study B was a single-center, open-label, randomized, single-dose, single-crossover study. Healthy volunteers received a tablet containing a combination of oxycodone 5 mg plus ibuprofen 400 mg after either an overnight fast of > or =8 hours or a standardized high-fat breakfast. Both studies included a washout period of > or =7 days between treatments. In both studies, the pharmacokinetic properties (C(max), T(max), t(1/2), AUC(0-4), AUC(0-1), and AUC(0-infinity)) of oxycodone and ibuprofen were derived from plasma drug concentrations. Analysis of variance was used to determine and compare pharmacokinetic properties. RESULTS: Twenty-four healthy, white, male subjects were included in study A (mean age, 26.0 years; mean body weight, 71.3 kg; mean height, 170.0 cm). Study B involved 12 subjects (11 men, 1 woman; mean age, 24.8 years; mean body weight, 77.2 kg; mean height, 181.4 cm). The pharmacokinetic properties of ibuprofen and oxycodone were not statistically different when administered alone or combined. Food intake did not affect the rate of oxycodone absorption (90% Cl of C(max) of fasted state vs fed state, 103-130), or the rate (90% Cl of C(max) of fasted state vs fed state, 72-95) or extent (90% Cl of AUC(0-infinity) of fasted state vs fed state, 88-102) of ibuprofen absorption. The extent of oxycodone absorption was slightly increased when the combination was given with food (90% Cl of AUC(0-infinity) of fasted state vs fed state, 115-127). CONCLUSIONS: The single-dose pharmacokinetic profiles of oxycodone and ibuprofen in these healthy volunteers were similar when these 2 drugs were given as monotherapy or in combination, suggesting bioequivalence. Food intake before administration of a single dose of the combination did not affect ibuprofen absorption but marginally increased the extent, but not the rate, of oxycodone absorption.

Administration, Oral↗

PubMed2002

Single-dose study to compare the pharmacokinetics of HFA flunisolide and CFC flunisolide.

The hydrofluoroalkane (HFA) formulation of the inhaled corticosteroid flunisolide is a modification of the original chlorofluorocarbon (CFC) formulation. HFA flunisolide replaces CFC with an HFA propellant and uses a built-in spacer in its pressurized metered-dose inhaler. The average HFA flunisolide particle size is 1.2 microm compared with 3.8 microm for the CFC formulation. The smaller particle size improves lung targeting, allowing a reduction in the HFA flunisolide dose relative to CFC flunisolide while maintaining comparable efficacy. In a study of 12 healthy men, pharmacokinetic parameters were determined after single doses of 1000 microg CFC flunisolide delivered without a spacer, 340 microg HFA flunisolide delivered through a spacer, and 516 microg HFA flunisolide delivered without a spacer. A standard noncompartmental analysis of the concentration data was performed and mean (+/- S.D.) pharmacokinetic values were reported. Peak plasma concentrations (observed C(max)) were similar for the three treatments. Area under the curve up to the time corresponding to the last measurable concentration (AUC(0)(-)(tlast)) was similar for the CFC and HFA flunisolide, plus spacer groups (4.4 +/- 1.6 ng x h/mL and 5.0+/- 4.2 ng x h/mL, respectively); however, AUC(0)(-)(tlast) for the HFA flunisolide without spacer group was comparatively lower than for the CFC group (3.5 +/- 1.6 ng x h/mL). Observed C(max) and AUC(0)(-)(tlast) for 6 beta-OH flunisolide, the first-pass metabolite of flunisolide and an indicator of oropharyngeal deposition, were significantly higher in the CFC flunisolide group than in either HFA flunisolide group.

Adolescent↗

PubMedDate not supplied

Multiple-dose proportionality study of flunisolide hydrofluoroalkane.

The hydrofluoroalkane (HFA) formulation of the inhaled corticosteroid flunisolide is a modification of the original chlorofluorocarbon formulation. HFA flunisolide substitutes an HFA for a chlorofluorocarbon propellant and uses a built-in spacer in its pressurized metered-dose inhaler. An open-label, randomized, three-way crossover, multiple-dose study evaluated the dose proportionality of three doses of flunisolide HFA. Twenty-one healthy volunteers received the following doses twice daily for 4.5 days: 85, 170, and 340 micrograms. Plasma levels of flunisolide and of the flunisolide metabolite 6 beta-OH flunisolide were measured after single- and multiple-dose administration. After a single dose, dose proportionality was observed across the three dose levels for peak plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) up to both the time corresponding to the last measurable concentration (AUC0-tau) and the time to infinity (AUC0-infinity). After multiple doses, dose proportionality was observed for both Cmax and AUC at the medium and high doses. Predose plasma levels of flunisolide measured on day 4 were below the limit of detection. The elimination half-life of flunisolide ranged from 0.95 to 1.34 hours. After both single and multiple doses, dose proportionality was observed in dose-adjusted Cmax and AUC0-infinity for the inactive 6 beta-OH metabolite. HFA flunisolide was well tolerated. The lack of accumulation after repeated administration of HFA flunisolide suggests that the systemic exposure of flunisolide is low, which is a safety goal for inhaled corticosteroids.

Administration, Inhalation↗