THE FIRST TWENTY YEARS (1994-2014) OF OZONE SOUNDINGS FROM RAPA NUI (27°S, 109°W, 51 M A.S.L.).

Ozone (O3) soundings have been performed on Easter Island or Rapa Nui (27°S, 23 109°W, 51 m a.s.l.) since 1994 as part of the Global Atmospheric Watch (GAW) Programme of the World Meteorological Organization (WMO). In this work, we analyze 260 soundings compiled over the period 1994-2014, and make the data available for the international community. We characterize O3 profiles over this remote area of the Pacific by means of statistical analyses that consider, on the one hand, a traditional climatology that describes the data in terms of seasonal cycles based on monthly averages and, on the other hand, a process oriented analysis based on self-organizing maps. Our analyses show the influence of both tropical and subtropical/mid-latitude air masses at Rapa Nui. The former occurs in summer and fall when convective conditions prevail, and the latter in late winter and spring when subsiding conditions are recurrent. The occurrence of stratospheric intrusions in late winter and spring in connection with deep troughs and the presence of the subtropical jet stream is also apparent in the data set. The tropospheric ozone column is in good agreement with the corresponding data derived from satellites but with a systematic overestimate of summer and fall values. We show evidence of an upward trend in ozone near the surface, which suggests the impact of local pollution. We look forward to an enhancement of the Rapa Nui observing site, given its location that offers a privileged position to observe climate change over the sparsely sampled and vast South Pacific Ocean.

Arthroscopic bone block metal-free fixation for anterior shoulder instability. Short-term functional and radiological outcomes. / Fijación artroscópica sin metal del bloque óseo en la inestabilidad anterior del hombro. Resultados funcionales y radiológicos a corto plazo.

INTRODUCTION: Anterior glenohumeral bone loss reconstruction reduces failure rates after soft tissue surgery in patients with large glenoid bone defects. Multiple bone block techniques have been described, most with metal hardware fixation. The objective of this study is to evaluate the safety, as well as the short-term functional and radiological results of an arthroscopic bone block metal-free fixation or bone block cerclage. MATERIAL AND METHODS: Retrospective study of patients with glenohumeral instability and>15% glenoid bone loss operated during 2019 with follow-up of at least 12 months. Radiography and computerized tomography studies were performed. Functional outcomes were evaluated before and after surgery with the Western Ontario Shoulder Instability Index and Rowe score. RESULTS: A total of 21 patients with a median age of 30.6 (SD 7.1) were included. All showed radiographic consolidation at 3 months follow-up. A percentage of 90.4 of bone grafts presented osteolysis at peripherical areas and 95.2% revealed consolidation in the areas with contact to the glenoid. The median glenoid estimated surface went from 79.3% before surgery to 98.4% at 12 months. Functional scores were statically significant (P<.001) for Western Ontario Shoulder Instability Index (35.6-86.9) and Rowe score (25.2 to 96.4). No serious complications were reported. CONCLUSION: The bone block cerclage is a safe, metal-free technique that achieves total consolidation of the bone graft and favorable functional and radiological outcomes at 12 months follow-up.

Fijación artroscópica sin metal del bloque óseo en la inestabilidad anterior del hombro. Resultados funcionales y radiológicos a corto plazo / Arthroscopic bone block metal-free fixation for anterior shoulder instability. Short-term functional and radiological outcomes

Introducción: Existen múltiples técnicas para la reconstrucción del defecto óseo glenoideo con bloque óseo en la inestabilidad glenohumeral anterior que reducen el riesgo de recidiva tras cirugía de partes blandas, la mayoría utilizando fijación metálica. El objetivo de este estudio es evaluar la seguridad quirúrgica y los resultados funcionales y radiológicos a corto plazo de los pacientes sometidos a una técnica artroscópica con bloque óseo y fijación sin metal. Material y métodos: Estudio retrospectivo de pacientes con inestabilidad y defecto óseo glenoideo>15% con 12 meses de seguimiento mínimo. Se sometieron a estudio radiográfico y tomografía axial computarizada. Se cumplimentaron escalas funcionales de manera pre y postoperatoria: el Western Ontario Shoulder Instability Index y la escala de Rowe. Resultados: Se incluyeron un total de 21 pacientes con una edad media de 30,6 (DE 7,1). Todos mostraron consolidación radiográfica a los 3 meses. El 90,4% de los injertos presentó osteólisis en las áreas más periféricas y el 95,2% presentó consolidación en las áreas de contacto con la glenoides. La media del área de superficie de la glenoides pasó del 79,3% preoperatoria al 98,4% a los 12 meses. Los resultados funcionales medios resultaron estadísticamente significativos (p<0,001) tanto para el Western Ontario Shoulder Instability Index (de 35,6 a 86,9) como para la escala de Rowe (de 25,2 a 96,4). No se presentaron complicaciones graves. Conclusión: La técnica de bloque óseo y fijación sin metal es un método de fijación seguro, sin componentes metálicos. Consigue una consolidación completa del injerto con buenos resultados funcionales y radiográficos a los 12 meses.(AU)

Introduction: Anterior glenohumeral bone loss reconstruction reduces failure rates after soft tissue surgery in patients with large glenoid bone defects. Multiple bone block techniques have been described, most with metal hardware fixation. The objective of this study is to evaluate the safety, as well as the short-term functional and radiological results of an arthroscopic bone block metal-free fixation or bone block cerclage. Material and methods: Retrospective study of patients with glenohumeral instability and>15% glenoid bone loss operated during 2019 with follow-up of at least 12 months. Radiography and computerized tomography studies were performed. Functional outcomes were evaluated before and after surgery with the Western Ontario Shoulder Instability Index and Rowe score. Results: A total of 21 patients with a median age of 30.6 (SD 7.1) were included. All showed radiographic consolidation at 3 months follow-up. A percentage of 90.4 of bone grafts presented osteolysis at peripherical areas and 95.2% revealed consolidation in the areas with contact to the glenoid. The median glenoid estimated surface went from 79.3% before surgery to 98.4% at 12 months. Functional scores were statically significant (P<.001) for Western Ontario Shoulder Instability Index (35.6-86.9) and Rowe score (25.2 to 96.4). No serious complications were reported. Conclusion: The bone block cerclage is a safe, metal-free technique that achieves total consolidation of the bone graft and favorable functional and radiological outcomes at 12 months follow-up.(AU)

Arthroscopic bone block metal-free fixation for anterior shoulder instability. Short-term functional and radiological outcomes / Fijación artroscópica sin metal del bloque óseo en la inestabilidad anterior del hombro. Resultados funcionales y radiológicos a corto plazo

Introduction: Anterior glenohumeral bone loss reconstruction reduces failure rates after soft tissue surgery in patients with large glenoid bone defects. Multiple bone block techniques have been described, most with metal hardware fixation. The objective of this study is to evaluate the safety, as well as the short-term functional and radiological results of an arthroscopic bone block metal-free fixation or bone block cerclage. Material and methods: Retrospective study of patients with glenohumeral instability and>15% glenoid bone loss operated during 2019 with follow-up of at least 12 months. Radiography and computerized tomography studies were performed. Functional outcomes were evaluated before and after surgery with the Western Ontario Shoulder Instability Index and Rowe score. Results: A total of 21 patients with a median age of 30.6 (SD 7.1) were included. All showed radiographic consolidation at 3 months follow-up. A percentage of 90.4 of bone grafts presented osteolysis at peripherical areas and 95.2% revealed consolidation in the areas with contact to the glenoid. The median glenoid estimated surface went from 79.3% before surgery to 98.4% at 12 months. Functional scores were statically significant (P<.001) for Western Ontario Shoulder Instability Index (35.6-86.9) and Rowe score (25.2 to 96.4). No serious complications were reported. Conclusion: The bone block cerclage is a safe, metal-free technique that achieves total consolidation of the bone graft and favorable functional and radiological outcomes at 12 months follow-up.(AU)

Introducción: Existen múltiples técnicas para la reconstrucción del defecto óseo glenoideo con bloque óseo en la inestabilidad glenohumeral anterior que reducen el riesgo de recidiva tras cirugía de partes blandas, la mayoría utilizando fijación metálica. El objetivo de este estudio es evaluar la seguridad quirúrgica y los resultados funcionales y radiológicos a corto plazo de los pacientes sometidos a una técnica artroscópica con bloque óseo y fijación sin metal. Material y métodos: Estudio retrospectivo de pacientes con inestabilidad y defecto óseo glenoideo>15% con 12 meses de seguimiento mínimo. Se sometieron a estudio radiográfico y tomografía axial computarizada. Se cumplimentaron escalas funcionales de manera pre y postoperatoria: el Western Ontario Shoulder Instability Index y la escala de Rowe. Resultados: Se incluyeron un total de 21 pacientes con una edad media de 30,6 (DE 7,1). Todos mostraron consolidación radiográfica a los 3 meses. El 90,4% de los injertos presentó osteólisis en las áreas más periféricas y el 95,2% presentó consolidación en las áreas de contacto con la glenoides. La media del área de superficie de la glenoides pasó del 79,3% preoperatoria al 98,4% a los 12 meses. Los resultados funcionales medios resultaron estadísticamente significativos (p<0,001) tanto para el Western Ontario Shoulder Instability Index (de 35,6 a 86,9) como para la escala de Rowe (de 25,2 a 96,4). No se presentaron complicaciones graves. Conclusión: La técnica de bloque óseo y fijación sin metal es un método de fijación seguro, sin componentes metálicos. Consigue una consolidación completa del injerto con buenos resultados funcionales y radiográficos a los 12 meses.(AU)

The Solar Spectrum in the Atacama Desert.

The Atacama Desert has been pointed out as one of the places on earth where the highest surface irradiance may occur. This area is characterized by its high altitude, prevalent cloudless conditions and relatively low columns of ozone and water vapor. Aimed at the characterization of the solar spectrum in the Atacama Desert, we carried out in February-March 2015 ground-based measurements of the spectral irradiance (from the ultraviolet to the near infrared) at seven locations that ranged from the city of Antofagasta (on the southern pacific coastline) to the Chajnantor Plateau (5,100 m altitude). Our spectral measurements allowed us to retrieve the total ozone column, the precipitable water, and the aerosol properties at each location. We found that changes in these parameters, as well as the shorter optical path length at high-altitude locations, lead to significant increases in the surface irradiance with the altitude. Our measurements show that, in the range 0-5100 m altitude, surface irradiance increases with the altitude by about 27% in the infrared range, 6% in the visible range, and 20% in the ultraviolet range. Spectral measurements carried out at the Izaña Observatory (Tenerife, Spain), in Hannover (Germany) and in Santiago (Chile), were used for further comparisons.

Correlation between beta-endorphin plasma levels and anginal symptoms in patients with coronary artery disease.

To verify whether beta-endorphin plasma levels influence the presence of anginal symptoms, 74 consecutive male patients were studied. All patients had previously documented coronary artery disease and reproducible exercise-induced myocardial ischemia. Thirty-five patients (Group I) had a history of angina and reported anginal symptoms during exercise stress testing; 39 patients (Group II) were asymptomatic and had documented silent myocardial ischemia during exercise. Baseline beta-endorphin plasma levels were measured in blood samples taken before exercise stress testing and analyzed by beta-endorphin-I125-RIA Kit-NEN (a radioimmunoassay method). The mean baseline beta-endorphin plasma level was 22.5 +/- 19 pg/ml in patients with anginal symptoms compared with 43.7 +/- 28 pg/ml in asymptomatic patients (p less than 0.001). Baseline blood pressure and heart rate-systolic pressure (rate-pressure) product at baseline and at ischemia threshold (1 mm ST segment depression) were similar in the two groups. Group II patients had a longer exercise duration (p less than 0.01), more pronounced ST segment depression (p less than 0.001) and a higher peak rate-pressure product (p less than 0.01). The extent of coronary artery disease, ejection fraction and left ventricular end-diastolic pressure were similar in the two groups. These data suggest that higher baseline beta-endorphin plasma levels may play a role in the decreased sensitivity to pain in patients with silent myocardial ischemia. In addition, different beta-endorphin levels can be associated with a different sensitivity to pain.

Central nervous system (CNS) leukemia: the role of high dose cytarabine (HDAra-C).

Knowing the good penetration of systemic HDara-C into the CNS, we treated with this approach overt meningeal leukemia, either isolated or with bone marrow (BM) disease, in 31 adults: 18 ALL, 4 ANLL, 1 lymphoid blast crisis of CGL (LBC-CGL), and 8 non-Hodgkin's lymphoma (NHL). Treatment consisted of Ara-C, 3 g/m2 i.v. q 12 h, by 3 h infusion for 8 doses, followed by 4 doses at day 21. Complete remitters received consolidation with four monthly 4-dose courses of HDara-C. Additional multidrug consolidation and direct CNS therapy with intrathecal (i.t.) methotrexate (MTX) or Ara-C +/- cranial RT was administered to the 11 remitters last treated. Twenty of 31 patients (64%) achieved CR: 10/10 with isolated meningeal leukemia and 10/21 with concurrent CNS and BM disease. Of the remaining 11 patients, 8 had cerebrospinal fluid (CSF) clearing with persistent BM disease. In all cases but one CNS symptoms resolved promptly. CR median duration was 6 months (range 2 to 20). The main toxicity was myelosuppression requiring intensive support. There was no neurologic toxicity. These results show that systemic HDara-C is highly effective in acute leukemias and NHL with CNS involvement, and suggest the utility of this regimen for sanctuary chemoprophylaxis in patients at high risk for CNS disease.

Optimization of sampling time for cyclosporine monitoring in transplant patients.

Cyclosporine (CsA) dosing is based on CsA plasma or blood concentrations measured 12 to 24 hours after drug administration (trough levels). This study evaluated the relationship between the timing of CsA concentrations and subsequent pharmacokinetic parameters to predict an optimal sampling period. Plasma samples were obtained from 22 patients before their morning dose of CsA and at 2, 4, 6, 8, 10, and 12 hours after the dose on the 7th and on the 21st day after heart transplantation. The plasma samples were assayed by both HPLC and FPIA. The Cmax for CsA was achieved over a period ranging from 2 to 6 hours (mean/median = 4.7/4.0) during the day 7 and the day 21 studies. The mean (+/- SD) half-life was 3.2 (1.0) hours on day 7 and 2.9 (1.1) hours on day 21, (P > 0.05); the mean apparent oral clearance was 276 (117) L/hr on the day 7 and 269 (209) L/hr on day 21, (P > 0.05). When CsA plasma concentration by either FPIA and HPLC was monitored, the drug concentration best correlated with AUC was found to correspond to the plasma samples taken 4 to 8 hours after drug administration. The authors conclude that through blood sampling for therapeutic drug monitoring of CsA is not optimal, and that further studies are necessary to correlate concentration monitoring during the dosing interval with pharmacologic and toxicologic parameters.

Dihydroquinidine versus disopyramide: efficacy in patients with chronic stable ventricular ectopy.

Dihydroquinidine (DQ) is contained in substantial amounts in quinidine salts, but its direct antiarrhythmic action has not been studied. The efficacy of oral DQ (300 mg t. i. d.) compared to disopyramide (D) (200 mg t.i.d.) was thus investigated using a double-blind crossover placebo-controlled protocol in 12 patients, aged 13 to 67 years, with chronic stable high frequency premature ventricular beats (PVB), defined as greater than 100 PVB/h during 48-72-h control Holter monitoring. The protocol included three 72-h treatment periods: DQ, D, and placebo at random. On days 2 and 3 of each period a 24-h Holter recording was carried out; drug blood levels were determined at peak (days 2 and 3) and trough time (day 3). No significant difference in the mean PVB/h was found between control (735 +/- 400) and placebo periods (564 +/- 388), or between the two Holter recordings of each period. Compared to placebo both DQ (106 +/- 113, p less than 0.005) and D (240 +/- 263, p less than 0.05) reduced the mean PVB/h, but the decrease was significantly higher with DQ (78 versus 53%, p less than 0.02). Nine patients (75%) on DQ and 5 (42%) on D had a greater than 70% decrease in mean PVB/h; complex PVBs were abolished in 3 of 6 patients on both treatments. On day 3, DQ plasma levels were 1.31 +/- 0.44 (peak) and 0.92 +/- 0.45 (trough) mg/l; D plasma levels were 2.88 +/- 0.64 (peak) and 2.02 +/- 0.31 (trough) mg/l; no significant difference was found between day 2 and day 3 samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefotaxime therapy of lower respiratory tract infections in intensive-care patients.

Cefotaxime is one of two third-generation cephalosporins (the other being ceftriaxone) that undergo significant metabolism and is the only third-generation cephalosporin for which an active metabolite has been identified. Cefotaxime was administered intravenously in doses of 6 g per day to 20 patients with serious infections of the lower respiratory tract due to organisms susceptible to cefotaxime (isolates of Enterobacteriaceae and of Pseudomonas aeruginosa). It was administered with gentamicin in some high-risk patients. Cefotaxime resulted in mean peak concentrations of 32 mu/ml (cv% = 53) and of 29.5 micrograms/ml (cv% = 65) respectively after the first and after the last dose of a regimen of 2 g every 8 hours. The half-life value averaged 1.8 h and 6.4 h for cefotaxime and its desacetyl metabolite respectively. The average value of the metabolite at the end of short infusion was 11.5 micrograms/ml (cv% = 31) after the initial dose and 15.5 micrograms/ml (cv% = 37) after the last administered dose. Overall results were 75% patients cured or improved; 83% of the patients with nosocomial pulmonary infections due to Enterobacteriaceae were cured; 50% of the patients with Pseudomonas aeruginosa infections were cured and 25% improved despite the pathogen not being eradicated. No serious toxicity was observed.

Dosing problems of gentamicin in critically ill patients.

Twenty critically ill patients with a diagnosis of possible or documented Gram-negative sepsis received gentamicin sulphate by i.v. short infusion (30 min). The same daily dose was administered in a variable frequency regimen (ten were treated by an 8 h frequency regimen and ten by a 12 h frequency regimen). Repeated measurements of gentamicin plasma levels and of serum creatinine, albumin, total proteins and haematocrit were performed simultaneously, with measurements of tubular casts, alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl-transpeptidase activity in urine. There was a considerable variation in plasma gentamicin concentrations among individuals patients and in the same patient from day to day with each dosage regimen. Despite the daily administration of at least 5 mg/kg/day of gentamicin, nephrotoxicity occurred in only one patient. The mean duration of therapy was about ten days. Although the series of patients was small, no significant difference was reported in either the 8 or 12 h dosage regimen in respect to favourable response to treatment among the patients. Probably a high peak concentration greatly exceeding the minimal inhibitory concentration (MIC) for a short duration, kills Gram-negative bacteria as effectively as a long concentration exceeding the MIC for a longer period of time. The reported half-lives and area under curve values for gentamicin in our patients varied widely even in the same patient.

Evaluation of the absorption from three ibuprofen formulations.

The pharmacokinetic differences between two sustained-release 300 mg (A) and 400 mg (B) formulations and a rapid-release 400 mg ibuprofen conventional sugar-coated formulation (C) were compared after a single dose. Mean peak levels of 25.1 micrograms/ml for preparation A (2 X 300 mg), 31.3 micrograms/ml for preparation B (2 X 400 mg) and 68.5 micrograms/ml for preparation C (2 X 400 mg) were reached at 5.3, 3 and 2 hours respectively, after ingestion of the drugs. The individual plasma-level time-profiles for the majority of doses suggested prolonged absorption of product A and B. The absorption from formulations A and B was significantly slower (p less than 0.001 and p less than 0.05 respectively) than that from the conventional tablets. The bioavailability of ibuprofen from sustained-release capsules, was not found to differ significantly from that of ibuprofen from conventional tablets. The relative bioavailability was very close to 100% in almost all subjects (coefficient of variation 14% and 17%). Projections of plasma concentrations upon multiple dosing were made from single dose data. The dosage interval concentration ratio which reflects both the frequency and the entry of the drug into and from the body was much lower for sustained-release formulations (A: 3.0; B: 3.7; C: 12.9).

Pharmacokinetics and clinical efficacy of indomethacin in premature infants with patent ductus arteriosus.

Despite a considerable amount of investigation, controversy continues concerning the use of indomethacin in inducing the closure of patent ductus arteriosus. This controversy may be attributable to differences in dosage, route of administration, postnatal age at treatment and the variable pharmacokinetics of the drug in premature infants. The pharmacokinetics and clinical efficacy of i.v. administered indomethacin in five premature infants with PDA were evaluated. There was considerable intersubject variability in the half life of elimination (63.1 +/- 38 h). This variability was mainly due to clearance (0.0086 +/- 0.0069 l/h/kg) rather than to distribution volume variability (0.54 +/- 0.27 l/kg). A reduction of half life was observed after the second dose, probably due to a maturation process. A permanent closure of the ductus was obtained in two patients after the first dose and in two patients after the second dose. The side-effects observed in our infants were transient and no long-term complication was attributable to this drug.

[Pharmacokinetics of ceftriaxone in the first three month of life]. / Farmacocinetica del ceftriaxone nei primi tre mesi di vita.

The purpose of the study was to define more precisely ceftriaxone kinetic variations in neonates and infants during the first three months of life. Ceftriaxone pharmacokinetics were studied in 14 newborns and infants with gestational age ranging from 31 to 42 weeks and younger than three months of postnatal age. Ceftriaxone was administered as an intravenous bolus injection over 15 min at a dose of 50 mg/Kg every 24 hours, for a period of 7 to 28 days according to the bacterial diseases. 13 patients had normal renal function and one had a chronic renal insufficiency. Plasma and urine concentrations were measured by a specific HPLC assay. The mean plasma concentration was 180.7 +/- 19.9 ug/ml (mean +/- SD) 30 min after the beginning of the infusion. After 24 h the plasma value was 29.9 +/- 10.0 ug/ml. The mean elimination half-life (t1/2) was 19.9 h, the total clearance (CL) of the drug was 0.38 ml/min/Kg and the volume of distribution (Vd) was 0.32 l/Kg. About 52% of the administered dose was excreted unchanged in urine. In the patient with renal insufficiency we observed t1/2 = 38.9 h and CL = 0.10 ml/min/Kg. Only a slight accumulation of the drug (from 180.7 +/- 19.9 ug/ml to 223 +/- 15.5 ug/ml) was observed during multiple dosing. The volume of distribution and the plasma half-life were significantly correlated (negative correlation) to the postnatal age. There was no correlation between clearance and postnatal age. No side effects were observed in newborns and infants after administration of ceftriaxone.

[The bioavailability of nicorandil after oral administration of a single dose of 10 or 20 mg preparations]. / Biodisponibilità del nicorandil dopo somministrazione orale in dose singola di preparati da 10 e da 20 mg.

To evaluate the bioavailability of 4 different formulations of nicorandil, 10 mg and 20 mg (Bracco) versus 10 mg ang 20 mg (Merck), we have carried out a study involving 24 young healthy volunteers. The drug was administered in single oral dose and the plasma concentration levels were evaluated by HPLC method. From the results obtained, we have seen that both the 2 products of 10 mg (A and B) and the 2 products of 20 mg (C and D) are equivalent and have high relative bioavailability: it reaches the values of 96.5% (A versus B) and 120% (C versus D). As regards the 2 formulation of 20 mg, the results of bioavailability are confirmed by data obtained from dissolution study in vitro, where the dissolution is almost complete in 30 minutes.

The role of psychologic stress in the genesis of lethal arrhythmias in patients with coronary artery disease.

To investigate the influence of psychologic stress on the electrophysiology of the heart and the genesis of cardiac arrhythmias, programmed ventricular stimulation was performed in 19 patients with recent uncomplicated myocardial infarction (37 +/- 10 days after the acute episode) during control conditions and during mental arithmetic. Psychological assessment showed a normal profile in all subjects. During mental stress, blood pressure increased (from 147 +/- 16/96 +/- 9 to 171 +/- 16/106 +/- 8 mmHg, P less than 0.001), and the mean ventricular refractory period decreased by 8 ms (1-3 extrastimuli P less than 0.05-0.001). Unsustained ventricular tachycardia (greater than or equal to 6 beats) was induced in 2 and 7 patients during control and during stress stimulation respectively (P less than 0.05). Ventricular fibrillation was provoked by double (1 patient) and triple (1 patient) extrastimuli during stress. In conclusion mental stress can induce measurable cardiac electrophysiological modifications in uncomplicated postinfarct patients and such modifications may favour the appearance of life-threatening arrhythmias.

The clinical pharmacology of drug interactions.

Preliminary evaluation of pre-established and extemporaneous combinations showed that any combination requires broad, precise, and scientifically valid documentation. Every drug has to be evaluated according to physical, chemical, and pharmacologic points of view, either individually or in combination, and above all be adapted to the individual needs of each patient. To make a realistic contribution to evaluating and devising new combinations, specialized centers should be instituted such as the Central Admixture Service of S. Matteo Hospital in Pavia.

Bioavailability of sustained-release theophylline formulations.

Sustained-release formulations of theophylline as well as of other drugs are designed to effect a delayed but constant release of the active principle in the gastrointestinal tract, thus ensuring more prolonged blood level curves. This study was made to assess the bioavailability of two sustained-release microencapsulated formulations and one sustained-release Diffucaps formulation, in comparison with an equivalent dose of theophylline solution. As regards bioavailability, none of the three formulations differed significantly from the reference formulation. The blood levels at steady state were estimated on the basis of data obtained after a single-dose study. All three sustained release formulations showed good results after prolonged administration in terms of peaks and troughs. The time duration at which the theophylline plasma levels remain higher than 75% of the maximum steady-state levels, following 12-h dosing interval, was evaluated: for the sustained-release microencapsulated formulations this time duration reaches 100% of the dosing interval. A multiple-dose administration of the sustained-release formulations used in this study should guarantee almost complete time coverage, with blood levels sharply exceeding the minimum threshold level of the theophylline therapeutic range.