A pharmacokinetic comparison of two oral liquid glucocorticoid formulations.

To compare pharmacokinetics of liquid prednisolone and prednisone solutions and to assess relative bioavailability, six healthy adult men were administered 15 mg of each formulation. Blood samples were obtained and assayed for plasma prednisolone concentrations by high-performance liquid chromatography. Peak concentration was significantly higher with liquid prednisolone (mean +/- SD 430.3 +/- 62.5 vs 333.0 +/- 27.8 ng/ml, p = 0.013), with similar times to peak concentration. Prednisolone liquid gave higher concentrations at every time point (statistically significant for all except 0.25 hrs after the dose), resulting in a significantly greater total area under the curve (2029.8 +/- 246.9 vs 1633.3 +/- 221.1 ng/ml.hour, respectively, p = 0.002). Clearance was slower for prednisolone (128.3 +/- 15.1 vs 149.1 +/- 17.6 ml/min/1.73 m2, p = 0.01), and the relative bioavailability of the prednisolone liquid using prednisone liquid as the reference standard was 116 +/- 14%. Thus, prednisolone liquid has similar pharmacokinetic characteristics as prednisone liquid, with improved bioavailability.

Inconsistent absorption from a sustained-release theophylline preparation during continuous therapy in asthmatic children.

During routine monitoring of hospitalized children with asthma receiving a sustained-release theophylline formulation, we frequently observe unpredictable fluctuations in serum theophylline concentration (STC). We evaluated eight asthmatic patients (ages 4 to 17 years) with inconsistent STCs to determine the cause of this phenomenon. Only minimal variation in STC and therefore theophylline clearance was noted during a 24-hour period of continuous intravenous aminophylline infusion. However, marked variability in STC was observed when measured every 2 hours for 48 hours after 6 days of continuous therapy orally. In addition, the time required to reach peak and trough STCs varied from dose to dose. Inasmuch as clearance was shown to be constant, the variability was attributed to inconsistent theophylline absorption. Unpredictable fluctuations of STC secondary to variable absorption from this sustained-release theophylline preparation may occur in certain patients. Appreciation of this potential variability is necessary for the proper interpretation of STC measurements and subsequent dosage adjustment.

Theophylline absorption from two sustained-release products. Implications for therapeutic drug monitoring.

Theophylline absorption from 2 sustained-release theophylline (S-RT) formulations was examined over 2 consecutive days during continuous therapy in 8 clinically stable hospitalized patients with moderate to severe asthma. Theo-24, a formulation intended for once-daily dosing, produced larger fluctuations in serum theophylline concentration (STC) than did twice-daily Theo-Dur (214 +/- 106% versus 89 +/- 33%, p less than 0.02). Bioavailability for both formulations was essentially complete over 2 consecutive study days (95 +/- 22% and 87 +/- 8% for Theo-Dur versus 88 +/- 21% and 87 +/- 24% for Theo-24 on Days 1 and 2, respectively). The time of maximal STC (Tmax) and minimal STC (Tmin) over a 24-h period were relatively predictable for Theo-24 with Tmax 6 to 14 h postdose, and Tmin occurring at the time of dose. However, only Tmax (4 to 10 h post-A.M. dose) was predictable for Theo-Dur. The mean maximal STC over a 24-h period (Cmax) for Theo-Dur was 13.9 (range, 8.9 to 20.7 micrograms/ml), whereas the mean 6-h post-AM dose STC was 13.0 (range, 8.0 to 20.7 micrograms/ml), indicating that the STC at this 6-h time point represents a very close estimate of the true Cmax. Similarly, the mean Cmax for Theo-24 was 14.5 (range, 6.2-20.4 micrograms/ml), and the mean 10-h post-dose STC was 13.7 (range, 3.6 to 20.4 micrograms/ml), suggesting that this time point approximates the true Cmax.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthmatic responses to airborne acid aerosols.

BACKGROUND: Controlled exposure studies suggest that asthmatics may be more sensitive to the respiratory effects of acidic aerosols than individuals without asthma. This study investigates whether acidic aerosols and other air pollutants are associated with respiratory symptoms in free-living asthmatics. METHODS: Daily concentrations of hydrogen ion (H+), nitric acid, fine particulates, sulfates and nitrates were obtained during an intensive air monitoring effort in Denver, Colorado, in the winter of 1987-88. A panel of 207 asthmatics recorded respiratory symptoms, frequency of medication use, and related information in daily diaries. We used a multiple regression time-series model to analyze which air pollutants, if any, were associated with health outcomes reported by study participants. RESULTS: Airborne H+ was found to be significantly associated with several indicators of asthma status, including moderate or severe cough and shortness of breath. Cough was also associated with fine particulates, and shortness of breath with sulfates. Incorporating the participants' time spent outside and exercise intensity into the daily measure of exposure strengthened the association between these pollutants and asthmatic symptoms. Nitric acid and nitrates were not significantly associated with any respiratory symptom analyzed. CONCLUSIONS: In this population of asthmatics, several outdoor air pollutants, particularly airborne acidity, were associated with daily respiratory symptoms.

Indoor air pollution and asthma. Results from a panel study.

Although there is abundant clinical evidence of asthmatic responses to indoor aeroallergens, the symptomatic impacts of other common indoor air pollutants from gas stoves, fireplaces, and environmental tobacco smoke have been less well characterized. These combustion sources produce a complex mixture of pollutants, many of which are respiratory irritants. We report here results of an analysis of associations between indoor pollution and several outcomes of respiratory morbidity in a population of adult asthmatics residing in the Denver, Colorado, metropolitan area. A panel of 164 asthmatics recorded in a daily diary the occurrence of several respiratory symptoms, nocturnal asthma, medication use, and restrictions in activity, as well as the use of gas stoves, wood stoves, or fireplaces, and exposure to environmental tobacco smoke. Multiple logistic regression analysis suggests that the indoor sources of combustion have a statistically significant association with exacerbations of asthma. For example, after correcting for repeated measures and autocorrelation, the reported use of a gas stove was associated with moderate or worse shortness of breath (OR, 1.60; 95% CI, 1.11-2.32), moderate or worse cough (OR, 1.71; 95% CI, 0.97-3.01), nocturnal asthma (OR, 1.01; 95% CI, 0.91-1.13), and restrictions in activity (OR, 1.47; 95% CI, 1.0-2.16). Among this panel of relatively moderate to severe asthmatics, the respiratory irritants produced by several domestic combustion sources were associated with increased morbidity.

Evaluation of nasal patency by fiberoptic rhinoscopy.

A novel method of assessing anterior nasal patency by flexible fiberoptic rhinoscopy was evaluated in two centers by comparison with active anterior rhinomanometry. Rhinoscopy and rhinomanometry were performed 20 times on each of 14 subjects during 14 to 26 minutes. The procedure was videotaped, and nasal airway area was measured from a video monitor. The mean coefficients of variation for rhinoscopy and rhinomanometry were 14% and 19%, respectively. Another investigator examined five subjects by rhinoscopy 30 times in 15 minutes; the mean coefficient of variation was 9%. These means were not significantly different. Rhinoscopy and rhinomanometry were performed at 30-minute intervals for a 6-hour period in 13 subjects. Three investigators independently evaluated results for changes in nasal function characteristic of the nasal cycle. Rhinoscopy detected the nasal cycle in an average of 72% of subjects and rhinomanometry in 49%. Both methods detected the response to topically applied oxymetazoline and methacholine. Results indicate that, whereas the two procedures evaluate different aspects of nasal function, their precision is similar. Rhinoscopy additionally permits evaluation of nasal mucosal changes occurring from disease or treatment.

Multicentre evaluation of disposable visual measuring device to assay theophylline from capillary blood sample.

A device using enzyme immunochromatography to indicate visually theophylline concentration in a small capillary blood sample was evaluated for precision and accuracy at four hospitals. Preliminary studies indicated sensitivity as low as 2.5 micrograms/ml, and accuracy and precision matched those in test samples ranging from 5 to 30 micrograms/ml. Absence of theophylline was also reliably detected. Paired samples of capillary and venous blood from 214 patients were used to compare this method with four standard laboratory assays. Correlations with the standard assays were 0.93-0.97, slopes 1.00-1.27, and y intercepts -1.91-0.46. The within-run coefficients of variation on twenty replicate patient sample analyses at the four hospitals were 5.1-9.7% and between-run coefficients of variation on a 15.9 microgram/ml control 5.7-9.4%. This disposable device for theophylline monitoring, which can be done within 15 min at the patient's side without instruments, is sufficiently accurate to replace laboratory analysis for routine therapeutic drug monitoring.

Comparison of parallel line skin test assay (PLST) and ELISA inhibition (EI) methods for determination of relative potency of polymerized grass and ragweed antigenic extracts.

Relative potency estimates were performed by parallel line skin test assay (PLST) and ELISA inhibition methods for three polymerized allergen extracts (Bermuda grass, orchard grass, and a copolymer of short and giant ragweed) versus four unmodified RAST standardized reference extracts (Bermuda grass, orchard grass, and giant and short ragweed) in nine subjects. One subject experienced a systemic reaction, requiring treatment at the end of the PLST assay. Another subject had a systemic reaction during limited skin testing performed approximately 72 hours after completion of PLST. Relative potency values for the polymerized extracts obtained by PLST were much lower than those obtained by ELISA inhibition, but results were significantly (r = 0.95; p less than 0.01) correlated. Because polymerized allergen extracts are designed to be hypoallergenic, a skin test assay may underestimate their potency relative to an unmodified reference extract.

Sensitivity to sulfited foods among sulfite-sensitive subjects with asthma.

Eight individuals with asthma who had been diagnosed as sulfite sensitive on the basis of double-blind capsule-beverage challenges were subjected to challenges with various sulfited foods, including lettuce, shrimp, dried apricots, white grape juice, dehydrated potatoes (as mashed potatoes), and mushrooms. Four of these patients failed to respond to challenges with any of the sulfited foods. The other four patients experienced a decrease in pulmonary function on double-blind challenges with sulfited lettuce. Two of three of these patients reacted to challenges with dried apricots and white grape juice; the fourth patient has not yet been challenged with these products. Only one of these four patients reacted to challenges with dehydrated potatoes and mushrooms, and, in this case, the response to double-blind challenges with dehydrated potatoes was not consistent. None of the sulfite-sensitive subjects with asthma responded to challenges with sulfited shrimp. It is concluded that sulfite-sensitive subjects with asthma will not necessarily react after ingestion of sulfited foods. The likelihood of a reaction is dependent on the nature of the food, the level of residual sulfite, the sensitivity of the patient, and perhaps on the form of residual sulfite and the mechanism of the sulfite-induced reaction.

Assessment of nasal patency by rhinoscopic measurement of cross sectional nasal airway area: correlation with subjective nasal symptoms.

Assessment of nasal patency by the recording of nasal symptom scores was compared with an objective method of determining nasal airway area using a fiberoptic rhinoscope. Sixty patients with active allergic rhinitis and nasal congestion requiring treatment were studied. Nasal symptoms were recorded and nasal airway area was measured before and at fixed time intervals after administration of either pseudoephedrine or oxymetazoline. Both methods detected a decongestant response to both drugs, and the symptom of congestion correlated with the measured nasal airway area. Rhinoscopic measurement of cross sectional nasal airway area is an objective method that may be used to complement other methods for evaluation of nasal patency.