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At least 19 recordsLinked to original sources
PubMed2001

Studies on the Biosynthesis of Paraherquamide: Synthesis and Incorporation of a Hexacyclic Indole Derivative as an Advanced Metabolite This work was supported by the National Institutes of Health (Grant no. CA70375 to R.M.W.). We wish to acknowledge the American Chemical Society Division of Organic Chemistry Fellowship (sponsored by SmithKline Beecham) and the Pharmacia-Upjohn Company for financial support (to E.M.S.). Mass spectra were obtained on instruments supported by the National Institutes of Health Shared Instrumentation Grant (No. GM49631). We also wish to thank Professor Dean Crick of the Department of Microbiology at Colorado State University for helpful discussions. J.F.S.-C. thanks the DGICYT of Spain for a research grant (project no. PB98-1438).

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Journal Article↗
PubMed1990

A report of three multiclinic trials evaluating arbaprostil in arthritic patients with ASA/NSAID gastric mucosal damage. The Upjohn Company Arbaprostil ASA/NSAID Gastric Mucosal Damage Treatment Study Groups.

Three randomized, placebo-controlled multiclinic trials involving arbaprostil dosages of (a) 10 micrograms; (b) 25 micrograms; and (c) 10, 25, or 50 micrograms orally for 4 wk in patients older than 18 yr with rheumatoid arthritis or osteoarthritis who had endoscopically documented nonsteroidal antiinflammatory drug-associated gastric mucosal damage were conducted in the United States. All patients continued taking the nonsteroidal antiinflammatory drugs and were reendoscoped after 4 wk of therapy. Success at that time was defined as complete resolution of all gastric mucosal damage. Six hundred fifty-eight patients were enrolled in the three trials. Significantly more patients experienced healing in the arbaprostil treatment groups in all trials compared with those who received placebo. The healing rates in the various trials were 68% and 32% (10 micrograms vs. placebo; p = 0.007); 77% and 23% (25 micrograms vs. placebo; p less than 0.001); and 52%, 46%, 35%, and 16% (50, 25, and 10 micrograms vs. placebo; p less than 0.001, less than 0.001, and 0.002, respectively). Diarrhea, mostly of a mild nature, was the only arbaprostil-associated side effect and was found with the 25- and 50-microgram dosages (33% and 59%, respectively). No exacerbation of arthritis signs or symptoms was found. Arbaprostil at doses with varying effects on gastric acid secretion (25 and 50 micrograms) was documented in these trials to be an effective and safe agent for healing gastric mucosal damage associated with aspirin or other nonsteroidal antiinflammatory drugs in patients with either rheumatoid arthritis or osteoarthritis without adversely affecting joint symptomatology.

Administration, Oral↗
PubMed1981

Alprazolam (Xanax, the Upjohn Company).

Alprazolam is a triazolobenzodiazepine, a derivative of the benzodiazepines. Comparison studies of alprazolam and diazepam or chlordiazepoxide in patients suffering from clinical anxiety secondary to anxiety neurosis or chronic alcohol withdrawal suggest an equal efficacy of those agents. Studies examining the use of alprazolam for the treatment of "primary depression" suggest that it is as effective as imipramine in the treatment of exogenous (reactive) depression. Although alprazolam may be effective in patients with exogenous depression, no extrapolation can be made to the treatment of endogenous depression. Mechanisms of action have not been fully elucidated, but probably are similar to those of other benzodiazepines. Peak blood levels are reached in 0.7-1.6 hours and the elimination half-life after steady state is approximately 19 hours. Daily dosages established from clinical studies ranged from 1 to 6 mg. Clinically, alprazolam appears to be ten times more potent than diazepam. Drowsiness, headaches, lightheadedness, dry mouth, and depression appear to be the most common side effects of the drug. It is concluded that alprazolam offers no striking therapeutic advantage over currently marketed benzodiazepines.

Adjustment Disorders↗
PubMed1982

Alprostadil (Prostin VR Pediatric Sterile Solution, The Upjohn Company).

Alprostadil is a naturally occurring prostaglandin used in the treatment of infants with congenital heart defects to maintain the patency of the ductus arteriosus until palliative or corrective surgery can be performed. In infants with defects restricting pulmonary blood flow (cyanotic), alprostadil improves arterial blood oxygenation. In infants with defects restricting systemic blood flow, alprostadil improves arterial blood pH, urine output, and femoral arterial pulses. Alprostadil is administered by continuous intraarterial or intravenous infusion, usually at a starting dose of 0.1 microgram/kg/min, with maintenance doses as low as 0.002 microgram/kg/min. The most common side effects include fever, apnea, flushing, bradycardia, hypotension, and seizures; although in some cases, some of these effects may be related to the infant's underlying condition. Literature reports of clinical experience with alprostadil are reviewed.

Alprostadil↗
PubMed1995

Survey results of POPS use in United States and Canadian schools of medicine and pharmacy.

Recent initiatives calling for changes in medical education, such as the General Professional Education of the Physician and Robert Wood Johnson Reports, have recommended alternative teaching approaches to the lecture format. The Patient-Oriented Problem-Solving (POPS) exercises, sponsored by the Upjohn Company (Kalamazoo, MI) and made available for pharmacology in 1985, offer one of many possible alternatives to lectures. The technique involves group interactions between four students in a working group, each of whom must, with the aid of their colleagues, arrive at mutual solutions to simulated cases in clinical pharmacology. The exercises are intended to complement and enhance the learning of concepts from lectures, and to help students apply these concepts practically. The system is used extensively by medical, pharmacy, and other health profession schools throughout the United States and also abroad, and many thousands of exercise booklets have been distributed free of charge by the Upjohn Company. Currently, a committee of the American Medical School Pharmacology (AMSP) group, working with Upjohn Company personnel, is responsible for overseeing the writing and educational testing of new and revised exercises. The purpose of this paper is to report the results of a survey of POPS use in medical and pharmacy schools in the United States, Canada, and Puerto Rico, completed in March 1993. The returns indicate continued strong interest in the approach, and the acquired data affirm its value in teaching principles of clinical pharmacology to students in basic pharmacology courses. Detailed data were obtained on patterns of use, and a number of advantages and disadvantages were identified. Priorities for the writing of new POPS exercises were expressed by the respondents. The information acquired will form the basis for planning new and revised POPS exercises in the future.

Canada↗
PubMed2000

The diagnostic validity and therapeutic value of lumbar facet joint nerve blocks with or without adjuvant agents.

Facet joints have been described as an important source of low back pain. The value of medial branch blocks in the diagnosis of facet joint mediated pain is considered important. However, the therapeutic value of medial branch blocks has not been determined. This study was designed to evaluate the duration of relief obtained and therapeutic value following controlled medial branch blocks with or without adjuvant agents Sarapin (High Chemical Company, Levittown, PA) and Depo-medrol (Pharmacia and Upjohn Company, Kalamazoo, MI). The study population consisted of 180 consecutive patients seen in a single pain management practice, divided into three groups with 60 patients in each group. Group I was treated with local anesthetic only, Group II with the addition of Sarapin, and Group III with the addition of Depo-medrol along with Sarapin. The prevalence of facet joint pain in chronic low back pain was determined as 36%, with a false-positive rate of 25%. Comparison of duration of relief in days with each block in the three groups showed that the relief was significantly superior in Group III compared with Group I and Group II, whereas Group II was superior to Group I.

Adult↗
PubMed1992

Steroids, the steroid community, and Upjohn in perspective: a profile of innovation.

The announcement in 1949 at the Mayo Clinic of the dramatic effect of cortisone in alleviating the symptoms of rheumatoid arthritis triggered a competitive worldwide research and development effort directed toward a single goal, the practical synthesis of the rare corticosteroids. The confluence of an extraordinary coalescence of multiple events and circumstances in the growth of the Upjohn Company with the Mayo discovery, inclusive of a pioneering role in the steroid field, conspired to create an environment ripe for innovation. The breakthrough, which gave Upjohn an early competitive edge, followed with startling swiftness. A common mold of the genus Rhizopus was found to introduce enzymatically an 11 alpha-hydroxyl group directly into the female hormone progesterone, which had just been synthesized from the soybean sterol stigmasterol--a one-step solution to the known multistep alternatives for 11-oxygenation. Retrospective analysis of this event in perspective with other key developments before and after at Upjohn and in the steroid community reveals a striking profile of ongoing innovation. A parallel scenario in kind was repeated at Upjohn a quarter century later. The sister soybean sterol sitosterol was radically degraded microbiologically and concurrently oxygenated in ring C to produce 9 alpha-hydroxyandrostenedione, an alternative key intermediate for corticoid synthesis. New chemical processes, highly integrated with existing processes, assured the continuation of Upjohn's leading role in steroid hormone production.

Cortisone↗
PubMed1994

Restructuring the total quality way--corporate quality leaders share their experiences. Interview by Lisa M. O'Rourke.

The pharmaceutical firm The Upjohn Company and the electronics giant and Malcolm Baldrige National Quality Award winner Westinghouse Electric Corporation have grappled with the challenge of keeping TQM on track during recent restructuring efforts. What these organizations have learned from the experience--as described here by Nicholas Andreatis, MD, Vice President of Upjohn's Corporate Quality Center, and Carl Arendt, Manager of Total Quality Services for Westinghouse's Productivity and Quality Center--can help healthcare organizations that are faced with the same challenges.

Drug Industry↗
PubMed1983

Maintenance of pregnancy in rabbits treated with long-lasting progestins.

Fertilized eggs from rabbits 1 or 2.5 days after insemination were transferred to the oviduct or uterine horn of recipients that had received a single subcutaneous injection of 20 or 30 mg of one of seven long-acting progestins. The rabbits were observed daily, and the number of implantation sites was determined 10 or 11 days after egg transfer. No implantation sites were recorded in the recipient does treated with progesterone or ZK-5623 (Schering AG, Berlin, West Germany), a nor-steroid compound. Thirty-nine percent and 51% of the transferred eggs implanted in the recipient does treated with ZK-5410 (Schering AG) and chloromadinone acetate (Eli Lilly & Company, Indianapolis, IN), respectively. However, most of the pregnant animals aborted 14 to 20 days after egg transfer. The pregnancy was either maintained to term or was prolonged beyond the normal gestation length in the does treated with other compounds, ZK-53915, ZK-9349 (Schering AG) or Depo-Provera (Upjohn Company, Kalamazoo, MI). The young delivered after a subcutaneous injection of 17 beta-estradiol and oxytocin were found normal and active.

Animals↗
PubMed2001

Tirilazad for acute ischaemic stroke.

BACKGROUND: Tirilazad mesylate is neuroprotective in experimental models of ischaemic stroke suggesting it might be of benefit clinically. OBJECTIVES: To assess whether tirilazad mesylate is safe and effective at improving outcome in patients with acute ischaemic stroke. SEARCH STRATEGY: Trials of tirilazad were identified from searches of the Cochrane Stroke Group Specialised Trials Register (last searched: May 2001) and the Cochrane Controlled Trials Register (CENTRAL/CCTR). In addition, we contacted the Pharmacia & Upjohn company, the manufacturer of tirilazad, to identify unpublished studies and further information. SELECTION CRITERIA: Truly and quasi-randomised unconfounded placebo or open controlled trials of tirilazad administered within 24 hours onset of suspected or proven acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Data relating to early and end-of-trial case fatality, disability (Barthel Index and Glasgow Outcome Scale), phlebitis, and QTc were extracted by treatment group from published data and company reports. MAIN RESULTS: Six trials (four published, two unpublished) assessing tirilazad in 1757 patients with presumed acute ischaemic stroke were identified; all were double-blind and placebo-controlled in design. Tirilazad did not alter early case fatality (odds ratio, OR 1.11, 95% confidence intervals, 95% CI 0.79 to 1.56) or end-of-trial case fatality (OR 1.12, 95% CI 0.88 to 1.44). Tirilazad increased the odds of being dead or disabled by about one fifth, though the result was only just statistically significant; the odds ratios were similar whether the expanded Barthel Index or Glasgow Outcome Scale were used to assess outcome (OR 1.23, 95% CI 1.01 to 1.51; OR 1.23, 95% CI 1.01 to 1.50 respectively). Tirilazad significantly increased the rate of infusion site phlebitis (OR 2.81, 95% CI 2.14 to 3.69). Functional outcome (EBI) was significantly worse in prespecified subgroups of patients: females (OR 1.46, 95% CI 1.08 to 1.98) and subjects receiving low dose tirilazad (OR 1.31, 95% CI 1.03 to 1.67); a non-significant worse outcome was also seen in patients with mild-moderate stroke (OR 1.40, 95% CI 0.99 to 1.98). REVIEWER'S CONCLUSIONS: Tirilazad mesylate increased the combined end-point of 'death or disability' by about one-fifth, but did not alter case fatality, when given to patients with acute ischaemic stroke. Although further trials of tirilazad are now not warranted, analysis of individual patient data from the trials may help elucidate why tirilazad appears to worsen outcome in acute ischaemic stroke.

Humans↗
PubMed1992

The pharmacokinetics of flurbiprofen in younger and elderly patients with rheumatoid arthritis.

The pharmacokinetics of flurbiprofen (Ansaid Tablets, Upjohn Company of Canada, Don Mills, Ontario) were evaluated in both younger (40 to 60 years) and elderly (65 to 83 years) rheumatoid arthritic patients after both a 100-mg single-dose administration and at steady state during a 100-mg twice-a-day dosage regimen. Both flurbiprofen plasma concentration-time profiles and the urinary excretion of flurbiprofen and its major metabolites were evaluated. The results indicate that the pharmacokinetics of flurbiprofen are linear in both age groups based on only minor changes between single-dose and steady-state parameter determinations and the agreement between calculated and predicted accumulation values in plasma concentrations. Only minor differences in the pharmacokinetic parameters were observed between the younger and elderly patients. Only free flurbiprofen clearance was found to have a significant but variable correlation to patient age. The effect of flurbiprofen on the urinary excretion of two prostaglandins were also evaluated throughout this study. In both age groups, the maximum decrease in urinary excretion was observed after the first dose, and this effect was maintained throughout the remainder of the study. Percent decreases from baseline in urinary excretion during drug administration were similar for both age groups. Similar side-effect profiles were observed between age groups.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

The influence of orlistat on the pharmacokinetics and pharmacodynamics of glyburide in healthy volunteers.

To assess the influence of orlistat on the pharmacokinetics and pharmacodynamics (the blood glucose-lowering effect) of glyburide, an open-label, placebo-controlled, randomized, two-way crossover study was done in 12 healthy male volunteers. Each subject received single 5-mg oral doses of glyburide (Micronase; The Upjohn Company, Kalamazoo, MI) on the fifth day of treatment with placebo (treatment A) and 80-mg orlistat (treatment B) three times a day for 4 1/3 days; the two treatments were separated by a five-day washout period. Serial blood samples were collected before and at appropriate intervals after each glyburide dose to determine plasma concentrations and blood glucose levels. Values of Cmax and AUC of glyburide showed an equality of the two treatments by the analysis of variance. There was an apparent correlation between blood glucose level and the logarithm of plasma glyburide concentration; this relationship appeared to not be altered when glyburide was administered with orlistat. In conclusion, orlistat administered at doses of 80-mg three times daily does not significantly alter the pharmacokinetics and blood glucose-lowering effect of a single 5-mg oral dose of glyburide in healthy volunteers.

Adult↗
PubMed1990

Synthesis of (1',2'-trans)-3-phenyl-1-[2'-(N-pyrrolidinyl)cyclohexyl]pyrrolid -2-ones as kappa-selective opiates.

(1',2'-trans)-3-Phenyl-1-[2'-(N-pyrrolidinyl)cyclohexyl]pyrrolid-2 -ones (1 and 2) and their 3,4-dichlorophenyl analogues (4 and 5) were synthesized as lactam analogues of U-50,488 (I; a kappa-opiate analgesic developed by Upjohn Company). Compounds 1 and 2 were found to be oxidized by air, in the presence of a strong base, to the 3-hydroxylated derivative 3. Compound 4 gave slightly higher kappa-affinity (Ki = 10 nM) than I, with about half the kappa-selectivity (mu/kappa = 23). Compounds 1 and 3 showed weaker kappa-binding (Ki = 400 nM), with about the same kappa-selectivity as 4. Compound 5, a diastereomer of 4, gave significantly weaker and less selective kappa-binding than 4; likewise, 2 is a weaker and less selective kappa-binder than 1. The binding data of intermediate compounds having the basic skeleton of I seem to reflect the importance of lipophilicity and the detrimental effects of bulky substituents on the amide nitrogen. It is likely that the binding conformation of I at the opiate receptors approaches that of the lactam analogue 4.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗