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Biomedical subjects

P Prasad

Publications and source records attributed to P Prasad.

At least 19 recordsLinked to original sources
PubMed2006

The relationship between specific tissue lesions and pain severity in persons with knee osteoarthritis.

INTRODUCTION: Pain is the most common symptom in knee osteoarthritis (OA), a leading cause of chronic disability, and a major source of the disability attributable to OA in general. Pain severity in knee OA is variable, ranging from barely perceptible to immobilizing. The knee lesions that contribute to pain severity have received little attention. OBJECTIVE: To examine whether worse pathology of specific knee tissues - i.e. cartilage, bone (attrition, cysts, bone marrow lesions, and osteophytes), menisci (tears and subluxation), ligaments, and synovium (synovitis/effusion) - is associated with more severe knee pain. METHODS: One hundred and forty-three individuals were recruited from the community with primary (idiopathic) knee OA, with definite tibiofemoral osteophytes in at least one knee, and at least some difficulty with knee-requiring activity. Knee magnetic resonance (MR) images were acquired using coronal T1-weighted spin-echo (SE), sagittal fat-suppressed dual-echo turbo SE, and axial and coronal fat-suppressed, T1-weighted 3D-fast low angle shot (FLASH) sequences. The whole-organ magnetic resonance imaging (MRI) scoring (WORMS) method was used to score knee tissue status. Since summing tissue scores across the entire joint, including regions free of disease, may dilute the ability to detect a true relationship between that tissue and pain severity, we used the score from the worst compartment (i.e. with the poorest cartilage morphology) as our primary approach. Knee pain severity was measured using knee-specific, 100 mm visual analogue scales. In analyses to evaluate the relationship between knee pain severity and lesion score, median quantile regression was used, adjusting for age and body mass index (BMI), in which a 95% CI excluding 0 is significant. RESULTS: The increase in median pain from median quantile regression, adjusting for age and BMI, was significant for bone attrition (1.91, 95% confidence interval (CI) 0.68, 3.13), bone marrow lesions (3.72, 95% CI 1.76, 5.68), meniscal tears (1.99, 95% CI 0.60, 3.38), and grade 2 or 3 synovitis/effusion vs grade 0 (9.82, 95% CI 0.38, 19.27). The relationship with pain severity was of borderline significance for osteophytes and cartilage morphology and was not significant for bone cysts or meniscal subluxation. Ligament tears were too infrequent for meaningful analysis. When compared to the pain severity in knees with high scores for both bone attrition and bone marrow lesions (median pain severity 40 mm), knees with high attrition alone (30 mm) were not significantly different, but knees with high bone marrow lesion without high attrition scores (15 mm) were significantly less painful. CONCLUSION: In persons with knee OA, knee pain severity was associated with subarticular bone attrition, bone marrow lesions, synovitis/effusion, and meniscal tears. The contribution of bone marrow lesions to pain severity appeared to require the presence of bone attrition.

Aged↗
PubMed2006

Evaluation of the pharmacokinetic interaction between fluvastatin XL and cyclosporine in renal transplant recipients.

OBJECTIVE: To assess the pharmacokinetic interaction between cyclosporine and extended-release fluvastatin (fluvastatin XL), 80 mg for 7 days, in stable renal transplant recipients. METHODS: This was a single-center, open-label study. 17 renal transplant recipients received their standard cyclosporine therapy (Days 1 - 9) plus a once-daily single oral dose of fluvastatin XL, 80 mg (Days 2 - 8). Blood samples were collected and cyclosporine (whole blood) and fluvastatin (plasma) concentrations determined by radioimmunoassay and HPLC fluorescence detection, respectively. Pharmacokinetic parameters were calculated using non-compartment analysis and fluvastatin results were compared with historical controls. RESULTS: Treatment with fluvastatin XL, 80 mg for 7 days, had no significant effect on either the AUC0-12 (3,644 ng x h/ml in the absence of fluvastatin vs. 3,534 ng x h/ml in the presence of fluvastatin) or the Cmax of cyclosporine (983 ng/ml in the absence of fluvastatin vs. 945 ng/ml in the presence of fluvastatin). Co-administration of fluvastatin XL also had no effect on the tmax, t1/2 or apparent clearance (CL/F) of cyclosporine in renal transplant patients. The AUC and Cmax for fluvastatin XL in the presence of cyclosporine (AUC0-24 1,192 ng. x h/ml, Cmax 271 ng/ml) were approximately 2-fold higher compared with historical data for fluvastatin XL alone in healthy volunteers (AUC0-24 630 ng x h/ml, Cmax 102 ng/ml) but lower than the historical data for fluvastatin IR, 40 mg b.i.d. alone in healthy volunteers (AUC0-24 1,340 ng x h/ml, Cmax 443 ng/ml). Tmax, t1/2 and trough levels of fluvastatin in the presence of cyclosporine were also similar to the historical controls. Concomitant administration of cyclosporine and fluvastatin XL was well tolerated by renal transplant recipients. CONCLUSIONS: Fluvastatin XL, 80 mg, and cyclosporine do not show clinically relevant pharmacokinetic interactions.

Administration, Oral↗
PubMed2006

Absorption characteristics of EC-MPS--an enteric-coated formulation of mycophenolic sodium.

UNLABELLED: Enteric-coated mycophenolate sodium is an advanced formulation delivering mycophenolic acid (MPA), designed to improve MPA-related upper gastrointestinal adverse events by delaying MPA release until the small intestine. OBJECTIVE: Two studies were undertaken to identify the absolute bioavailability and dose-proportionality of enteric-coated mycophenolate sodium in stable renal transplant patients receiving cyclosporine. METHODS: Study 1: The mean MPA AUC(0-t) was shown to be greater after MPA infusion than after oral enteric-coated mycophenolate sodium (42.1 vs. 28.9 microg x h/ml). Mean absolute bioavailability was 0.71 +/- 0.21 (SD). Study 2: The AUC(0-t) and C(max) for MPA were proportional to the dose of enteric-coated mycophenolate sodium, similarly mean AUC(0-infinity) and C(max) for MPA glucuronide were proportional to dose administered. RESULTS AND CONCLUSIONS: In patients receiving cyclosporine the absolute bioavailability of MPA provided by enteric-coated mycophenolate sodium is equivalent to that provided by mycophenolate mofetil when administered in combination with cyclosporine, and exhibits dose-proportionality. Enteric-coated mycophenolate sodium was well tolerated from 180 - 2,160 mg with no serious adverse events reported.

Administration, Oral↗
PubMed2004

Correlation of percutaneous liver biopsy fragmentation with the degree of fibrosis.

BACKGROUND: Although fragmentation of a liver biopsy specimen has been considered to be suggestive of cirrhosis, the evidence for this is difficult to find in the published literature. AIM: To determine whether fragmentation of percutaneous liver biopsy specimens correlates with the degree of fibrosis. METHODS: One hundred and eighty-six patients underwent percutaneous liver biopsy prospectively. The specimens were measured for the length and number of fragments. The extent of fibrosis was scored by a pathologist blind to the clinical data. Length and fragmentation data were compared between the different stages. RESULTS: The overall median fragment length was 1.85 cm and the median fragment number was four. Specimens with advanced fibrosis (stages III-IV) had more fragments than those with no or mild fibrosis (stages 0-II) (P < 0.0001). The aggregate fragment length decreased with increasing stage of fibrosis (P < 0.0001). Specimens with greater than 12 fragments were seen only with advanced fibrosis. CONCLUSIONS: Fragmentation of percutaneous liver biopsy specimens is common and increases with progression from early to advanced fibrosis. Fibrotic specimens fragment more often and more extensively.

Adult↗
PubMed2004

Steatosis and fibrosis in patients with chronic hepatitis C.

BACKGROUND: Steatosis is present on liver biopsy in approximately 50% of patients with hepatitis C; its association with stage of fibrosis has been reported, but its relation to other fibrosis associated factors is unknown. AIM: To study the relation between steatosis and other histological features in patients with hepatitis C, and changes in steatosis with time. METHODS: Cross sectional study: 233 routine liver biopsies from 219 patients with hepatitis C; hepatectomy specimens from 65 patients transplanted for hepatitis C cirrhosis. Longitudinal study: 41 patients with two biopsies and 10 patients with three biopsies performed over 2-8 years. Biopsies were scored by the Ishak scheme, and degree of steatosis assessed subjectively. Multivariate analysis was used to study the interaction of fibrosis associated factors. Changes in steatosis over time in individual patients were explored in the longitudinal study. RESULTS: Steatosis was present in 50% of biopsies. It correlated strongly with fibrosis in non-cirrhotic samples, but declined in cirrhosis, and was unusual in transplant hepatectomy specimens. On multivariate analysis of non-cirrhotic biopsies, steatosis was associated with increasing patient age and remained significantly associated with fibrosis independent of portal inflammation and interface hepatitis. In the longitudinal study, steatosis persisted and increased over time, except in patients developing cirrhosis. CONCLUSIONS: Steatosis is associated with fibrosis independently of necroinflammation, but declines in cirrhosis. It may represent a pathogenic pathway distinct from necroinflammatory activity in the generation of liver fibrosis, and should be included in the assessment of biopsies for clinical and research purposes.

Adolescent↗
PubMed2004

Is endosonography guided fine needle aspiration (EUS-FNA) for sarcoidosis as good as we think?

BACKGROUND: Preliminary data show that endosonography guided fine needle aspiration (EUS-FNA) may be an accurate method for diagnosing sarcoidosis. However, these data were obtained in a small selected group of patients with a very high pretest probability of sarcoidosis. This retrospective study reports on the use of EUS-FNA in an unselected group of patients with mediastinal lymphadenopathy of unknown origin. METHODS: The EUS database of a single tertiary referral centre was reviewed for patients who underwent EUS-FNA for mediastinal lymphadenopathy of unknown origin. Clinical presentation and imaging studies of each case were carefully reviewed and the diagnosis "sarcoidosis" or "no sarcoidosis" attributed if possible. The diagnoses were compared with the result of EUS-FNA. RESULTS: One hundred and twenty four patients were investigated. In 35 cases EUS-FNA identified granulomas (group 1); in the other 89 cases (group 2) no granulomas were detected. The definite diagnoses in group 1 were sarcoidosis (n = 25), indefinite (n = 7), no sarcoidosis (n = 3). The definite diagnoses in group 2 were sarcoidosis (n = 3), indefinite (n = 9), no sarcoidosis (n = 77). Of the 77 cases with no sarcoidosis, 44 were diagnosed with other diseases. The other 33 showed non-specific changes in the FNA and sarcoidosis was excluded by negative non-EUS pathology (n = 17) and clinical presentation. The sensitivity and specificity for EUS-FNA were 89% (95% CI 82 to 94) and 96% (95% CI 91 to 98), respectively, after exclusion of the indefinite cases in both groups. CONCLUSIONS: EUS-FNA is an accurate method for diagnosing sarcoidosis in an unselected group of patients with mediastinal lymphadenopathy. The reported sensitivity and specificity must be appreciated in the context of the difficult and often incomplete clinical diagnosis of sarcoidosis.

Adult↗
PubMed2003

Training in radial EUS: what is the best approach and is there a role for the nurse endoscopist?

BACKGROUND AND STUDY AIMS: The aim of this study was to determine the relative contribution of previous endoscopic experience, case observation, and hands-on experience to skill acquisition in radial EUS. METHODS: In EUS trainees, four senior gastroenterology fellows, and a nurse endoscopist, the ability to reproduce set views from the mediastinum, stomach, and duodenum was assessed. Points were ascribed to static and dynamic stations and to the use of console controls. RESULTS: Trainees observed 55 - 170 cases and conducted 25 - 124 examinations. Competence was demonstrated after performing approximately 25 examinations in the mediastinum, 35 examinations in the stomach, and 78 examinations in the duodenum. The number of previous examinations conducted correlated with the ability to scan the duodenum ( P < 0.01). Observation of 100 or more further procedures early in training did not accelerate learning. The nurse endoscopist showed a comparable degree of competence in mediastinal scanning to that of the other trainees after performing a similar number of examinations. CONCLUSIONS: Proficiency in radial endosonography is greatly influenced by the numbers of examinations performed. Observing large numbers of cases early in training does not appear to translate into competence. A background in advanced therapeutic endoscopy is not a prerequisite for acquiring endoscopic ultrasound skills. Nurse endoscopists may be expected to train successfully in mediastinal imaging at the same pace as senior gastroenterology fellows.

Adult↗
PubMed2003

Upper gastrointestinal endoscopy performed by nurses: scope for the future?

BACKGROUND: Previous researchers have shown that non-medical endoscopists can perform lower gastrointestinal endoscopy as safely and effectively as medical staff. However, it is not known if upper gastrointestinal endoscopy performed by medical and non-medical endoscopists in clinical practice yields similar results in terms of performance, patient discomfort, and satisfaction. AIM: To determine differences in the yield of diagnosis for significant disease during upper gastrointestinal endoscopy performed by nurse and medical endoscopists and to measure patient discomfort, satisfaction, and attitudes towards future endoscopy. PATIENTS: This two part study included 3009 patients in a retrospective analysis and 480 in a prospective study. METHODS: The first part of the study assessed indications for endoscopy, diagnoses, and procedures performed by medical and nurse endoscopists. In a second prospective study, 480 patients were included to determine the association between endoscopist type and sedation, patient anxiety, discomfort, satisfaction, and attitudes towards future sedation. RESULTS: No patient refused endoscopy by either a nurse or medical endoscopist and there were no complications in either group. Nurses performed 1487 procedures and reported fewer endoscopies as "normal" than medical staff (p=0.006). Multivariate analysis showed that male sex, older age, inpatient status, dysphagia, and gastrointestinal bleeding, but not endoscopist type, were all associated with significant disease. In relation to discomfort and satisfaction, a similar proportion of patients received sedation in both groups (p=0.81). There were no differences in pre-procedure anxiety (p=0.61), discomfort during intubation (p=0.97), discomfort during examination (p=0.90), or post-procedure examination rating (p=0.79) in patients examined by medical or nurse endoscopists. CONCLUSION: Experienced nurses perform routine diagnostic gastroscopy safely in everyday clinical practice and with as little discomfort and as much patient satisfaction as medical staff.

Age Factors↗
PubMed2002

Safe administration of etoposide phosphate after hypersensitivity reaction to intravenous etoposide.

Etoposide is commonly used in a variety of malignancies. A well known but rare toxicity are hypersensitivity reactions, usually manifested by chest discomfort, dyspnoea, bronchospasm and hypotension. We report the details of a patient who developed hypersensitivity reactions to intravenous etoposide, but subsequently tolerated the administration of intravenous etoposide phosphate with no sequelae.

Adult↗
PubMed2001

Comparison of echocardiography with technetium 99m-gated single photon emission computed tomography as diagnostic tools for left ventricular ejection fraction.

Left ventricular ejection fractions (LVEF) are routinely measured and result in critical decision-making algorithms in cardiology. This study was conducted to compare the accepted standard two-dimensional (2-D) echocardiogram ejection fraction (EF(ECHO)) with single photon emission computed tomography rest ejection fraction (EF(SPECT)). Data were acquired and analyzed from 51 inpatients. EF(ECHO) was obtained using modified Simpson's rule in the four-chamber apical view, and gated EF(SPECT) was computed by an automated method (Siemens ICON software). Comparison between EF(ECHO) and EF(SPECT) was done by linear regression, Bland-Altman, and receiver operator characteristic (ROC) analyses. Linear regression analysis revealed EF(SPECT) = 1.12 x EF(ECHO) - 3.6%, r = 0.93, n = 51, P < 0.0001. Bland-Altman analysis showed that the limits of 95% confidence for the difference between EF(SPECT) and EF(ECHO) were - 12% to 18%. Ninety-eight percent of the datapoints were within the limits of confidence. The ROC analysis showed that the sensitivity and specificity for detecting abnormal EF (< or = 50%) were 85% and 86% with EF(SPECT), and 91% and 90% with EF(ECHO). This study showed good correlation as well as agreement between SPECT and two-dimensional echocardiograms in measuring EF.

Coronary Artery Disease↗
PubMed2001

Safety, tolerability, and pharmacokinetics of an extended-release formulation of fluvastatin administered once daily to patients with primary hypercholesterolemia.

Fluvastatin sodium (Lescol, Novartis Pharmaceutical Corp., East Hanover, NJ, U.S.A.), a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co-A) reductase inhibitor that limits cholesterol biosynthesis, is available as a 40-mg immediate-release formulation capsule. An extended-release formulation for once-daily administration has been developed for patients with primary hypercholesterolemia who may benefit from doses higher than 40 mg/day. This phase I study evaluated the safety, tolerability, and pharmacokinetics of a new fluvastatin extended-release formulation at doses ranging from 80-640 mg/day in 40 hypercholesterolemic patients. After a 2-week dietary stabilization phase, patients (Fredrickson type IIa/IIb), 18-55 years of age, were randomly assigned to four groups to receive oral fluvastatin extended-release (80, 160, 320, or 640 mg) or matching placebo once daily for 13 days. Fluvastatin extended-release was generally safe and well tolerated at doses of 80-320 mg/day. Within this dose range, linear pharmacokinetics was observed after single and multiple dosing. At 640 mg, fluvastatin extended-release was not well tolerated. Six of the seven actively treated patients at this dose experienced adverse events, including diarrhea, headache, and clinically relevant elevations in serum transaminase concentrations. In addition, nonlinear pharmacokinetics, possibly due to saturation of first-pass metabolism, was observed at this dose, causing higher than expected serum drug concentrations. Once-daily administration of fluvastatin extended-release at doses of 80-320 mg/day was generally safe and well tolerated in patients with primary hypercholesterolemia over a 13-day dosing period.

Adolescent↗
PubMed2001

Single-stage lumbar sympathectomy and omentopexy: a new surgical approach towards patients with Buerger's disease.

Single-stage lumbar sympathectomyand omentopexy were performed in six patients with Buerger's disease at the Department of Surgery, Jawahar Lal Nehru Medical College and Hospital, Ajmer, India, between January 1994 and December 1996. All were male smokers and had limb coldness, intermittent claudication and rest pain. Four had limb discoloration and three had ulcers of toes unresponsive to medical treatment. Postoperatively there was relief of symptoms in all, with improvement of tissue oxygen saturation and increase in claudication distance. We conclude that single-stage lumbar sympathectomy and omentopexy is an effective new surgical approach towards patients with Buerger's disease.

Adult↗
PubMed2000

Pedicled omental transfer for limb salvage in Buerger's disease.

We performed pedicled omental transfer in 62 patients with Buerger's disease at the Department of Surgery, J.L.N. Hospital, Ajmer between January 1990 and December 1996. All were male and had evidence of limb ischaemia. Post-operative results in these patients consisted of relief of intermittent claudication in 92%, disappearance of rest pain in 94%, disappearance of limb coldness in 83%, disappearance of discolouration in 82%, and healing of ischaemic ulcers in 83%. Tissue oxygen saturation in the affected limb improved from a mean of 84.8+/-3.6% in the preoperative period, to 89+/-1.5% at 12 h, 93.1+/-1.8% at 72 h and 96+/-1.2% at the end of 2 months of follow-up. Claudication distance improved from a mean of 75+/-20 m in the pre-operative period to 1000+/-110 m at 2 months of follow-up in 57 of 62 patients. Major amputations were not required in any patient, thus conserving the limb. We conclude that pedicled omental transfer offers promising results in patients with limb ischaemia due to Buerger's disease.

Adult↗
PubMed2000

Effects of furosemide on medullary oxygenation in younger and older subjects.

UNLABELLED: Renal medullary hypoxia is characteristic of mammalian kidneys and can be assessed noninvasively in animals and humans by blood oxygen level-dependent magnetic resonance imaging (BOLD MRI). Water diuresis has been shown to improve medullary oxygenation in young human subjects but not in elderly subjects, a difference attributed to a decline in renal prostaglandin production with age. Loop diuretics such as furosemide also increase medullary oxygenation in experimental animals, by inhibiting active transport and oxygen consumption in the medullary thick ascending limb. We examined, using BOLD MRI, this response to furosemide in eight younger (23 to 34 years) and eight elderly (64 to 81 years) healthy women. We also attempted to assess the role of prostaglandins in age-related differences, using ibuprofen to inhibit prostaglandin E2 synthesis. Renal medullary oxygenation, initially low, increased during furosemide diuresis in younger subjects. In the older population, however, furosemide usually elicited little or no change in oxygenation of the renal medulla, despite profuse diuresis. Ibuprofen did not inhibit the action of furosemide to improve medullary pO2 in younger subjects. CONCLUSIONS: The action of loop diuretics to improve medullary oxygenation, apparent in younger subjects, is blunted by normal aging. Inhibition of prostaglandin synthesis did not counteract the effect of furosemide in younger subjects, suggesting that a decline in prostaglandin E2 production with age is not the central cause of this age-related defect.

Adult↗
PubMed2000

Effect of intra-tracheal instillation and inhalation of silicon dioxide on some biochemical variables in broncho-alveolar lavage fluid and lung histopathology in rats.

In the present study, the bronchial alveolar lavage fluid (BALF) biochemical and lung histopathological changes occurring in response to single large intra-tracheal exposure to silica have been compared to the changes seen after continued chronic exposure via inhalation. Male albino rats (200-250gms) were exposed to silicon dioxide via intratracheal instillation (8mg/0.05ml saline) and whole body inhalation (200mg/m3, 6 hours/day for 2 and 4 weeks) in separate groups . The respective control animals were instilled with normal saline (0.05ml) or exposed to fresh air in simulation chamber for the same duration. BALF was analyzed for total protein, elastase, malondialdehyde (MDA) levels and catalase activity and histopathology of right lung was carried out after 4 weeks post-exposure in intra-tracheal model and after 2 and 4 weeks of exposure in the inhalation model. The levels of total protein, elastase and malondialdehyde (MDA) were significantly elevated, while catalase activity was significantly decreased in the BALF of exposed animals as compared to controls. The histopathological studies of lungs, showed exudates of inflammatory cells, chiefly of macrophages in the alveolar spaces and interstitial septa with multifocal nodular granulomatous lesions. The biochemical findings in BALF of both the models indicate inflammatory changes, lipid peroxidation and fibrosis. However, comparatively lower catalase activity and higher elastase levels in the 4 week inhalationally exposed group than the 4 week post intratracheally exposed group, suggests that these parameters may be affected by acute and chronic exposure and require further confirmation.

Animals↗
PubMed2000

Abdominal tuberculosis in children: an Indian experience.

The hospital records of 125 children, aged 14 years or less treated for abdominal tuberculosis (TB) at Jawahar Lal Nehru Medical College and Hospital, Ajmer, India between January 1987 and December 1996, were studied to analyse the various patterns of abdominal TB in children and to evaluate the role of various investigations in researching a diagnosis. Abdominal pain was the presenting symptom in 100 (80 per cent) patients. Detectable ascites was present in 55 (44 per cent) and visible peristalsis in 45 (36 per cent) cases. Laboratory investigations and radiographs were not conclusive in the majority of the patients. In 45 (36 per cent) patients in whom no tissue diagnosis was available, the diagnosis was based on a dramatic clinical response to anti-tuberculous chemotherapy. Fifty (40 per cent) patients were treated conservatively with anti-tuberculous drugs alone; the remaining patients underwent laparotomy for diagnosis and relief of bowel obstruction. There were no post-operative deaths and on follow-up, good recovery was observed in these patients. Abdominal TB in children is of a non-specific nature and defies diagnosis with non-invasive investigations; laparotomy is required for a definitive diagnosis in the majority of the patients. However, if a high index of suspicion is maintained in endemic areas, a therapeutic trial of anti-tuberculous chemotherapy is justified.

Abdominal Pain↗
PubMed2000

Pharmacokinetics, pharmacodynamics, and safety of microencapsulated octreotide acetate in healthy subjects.

The pharmacokinetics, pharmacodynamics, and safety of the marketed formulation of microencapsulated octreotide acetate were evaluated in an open-label study in 22 healthy cholecystectomized subjects. Each subject received a single 30 mg dose of microencapsulated octreotide acetate intramuscularly (i.m.). Concentrations of octreotide, growth hormone (GH), insulin-like growth factor binding protein 3 (IGFBP-3), and insulin-like growth factor 1 (IGF-1) as well as clinical safety were evaluated over a period of 112 days (16 weeks). After the injection, mean serum octreotide concentration initially increased rapidly, reached the maximum (Cmax, day 1 = 0.96 +/- 0.25 ng/ml) approximately 1.5 hours after dosing, and declined thereafter until 24 hours postdose (Cmin, 24 h = 0.088 +/- 0.093 ng/ml). The octreotide concentration then increased and started a sustained release from day 7 onward. Plateau concentrations were maintained through day 70 and gradually declined to below the lower limit of quantification (LLOQ) by day 112. The plateau height (Cplateau (2-112d, 60%)) was 1.68 +/- 0.88 ng/ml, and the duration (delta plateau, 60%) was 30.2 +/- 15.7 days. The integrated concentration-time curve, AUC0-112d, was 2819 +/- 782 (ng.h/ml), and the apparent half-life (t1/2) was 169 hours. To assess the variability, the drug concentrations were determined hourly for 8 hours on day 28, and the mean octreotide concentration, Cavg, day 28' was 1.55 +/- 1.26 ng/ml. The suppression of IGF-1 was statistically significant compared to the baseline (p < 0.05) through day 63; however, there were no appreciable changes in GH and IGFBP-3 concentrations after a single injection of microencapsulated octreotide acetate. Simulation of a 28-day dose schedule suggested that steady-state octreotide concentrations would be reached by the third injection with steady-state concentrations about twofold greater than the first injection. There were no serious adverse events or clinically meaningful changes in vital signs, ECGs, or laboratory evaluations observed in this study, indicating that the 30 mg i.m. dose of microencapsulated octreotide acetate was well tolerated in this population.

Abdominal Pain↗