PubMed Health⌕ Search

Biomedical subjects

P D Goldenheim

Publications and source records attributed to P D Goldenheim.

At least 19 recordsLinked to original sources
PubMed1999

Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for the purpose of titrating to stable pain control?

Two separate trials compared controlled-release (CR) oral oxycodone (administered every 12 hours) with immediate-release (IR) oxycodone (4 times a day) to determine whether patients with chronic pain could be titrated to stable pain control as readily with the CR as with the IR formulation. In one study, 48 patients with cancer pain were randomized to open-label titration with either CR or IR oxycodone (maximum dose, 400 mg/day) for a period of up to 21 days. In a study of similar design, 57 patients with low back pain were titrated with either CR or IR oxycodone (maximum dose, 80 mg/day) for a period of up to 10 days. The majority of patients in both studies were converted to oxycodone from other opioid analgesics. Results of both studies showed no difference between CR and IR oxycodone with respect to both the percentage of patients achieving stable pain control, the time to achieve stable pain control, and the degree of pain control achieved. Among cancer patients, 85% achieved stable analgesia, 92% with the CR formulation and 79% with the IR formulation. Among noncancer patients, 91% achieved stable pain control, 87% with the CR formulation and 96% with the IR formulation. The most commonly reported adverse effects in both studies were similar for the two formulations and were those anticipated with opioids: nausea, vomiting, constipation, somnolence, dizziness, and pruritus. Nausea and vomiting were the most frequently cited reasons for treatment discontinuations. These studies suggest that dose titration can be accomplished as readily with oral CR oxycodone as with IR oxycodone in patients with chronic, moderate to severe pain.

Adult↗
PubMed1996

Analgesic efficacy of controlled-release oxycodone in postoperative pain.

The efficacy and safety of graded doses (10, 20, and 30 mg) of controlled-release (CR) oxycodone was compared with that of immediate-release (IR) oxycodone (15 mg), immediate-release oxycodone 10 mg in combination with acetaminophen 650 mg (APAP), and placebo in a single-dose, double-blind, randomized, parallel-group study. The participants, 182 inpatients experiencing moderate to severe pain after abdominal or gynecologic surgery, provided hourly ratings of pain intensity and relief for 12 hours after administration. All active treatments were significantly superior to placebo for many hourly measurements and for the sum of pain intensity differences (SPID) and total pain relief (TOTPAR). A dose response was found among the three levels of CR oxycodone for pain relief and peak pain intensity difference (PID), with the 20- and 30-mg doses being significantly better than the 10-mg dose. For all active treatments, peak PID and peak pain relief occurred approximately 2 to 4 hours after administration. The median time to onset of relief was 32 minutes for oxycodone plus APAP, 41 minutes for IR oxycodone, and 46 minutes for CR oxycodone 30 mg. Duration of pain relief showed that the 10-, 20-, and 30-mg doses of CR oxycodone had durations of action of 10 to 12 hours compared with IR oxycodone and oxycodone plus APAP (both approximately 7 hours). Typical adverse events, particularly somnolence, occurred in all active treatment groups. Treatment with CR oxycodone was safe and effective in this study, and its characteristics will be beneficial in the treatment of pain.

Acetaminophen↗
PubMed1996

Pharmacokinetic-pharmacodynamic relationships of controlled-release oxycodone.

Plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined after administration of 20 mg oral controlled-release oxycodone tablets to four subject groups: young (aged 21 to 45 years) men, elderly (aged 65 to 79 years) men, young women, and elderly women. Area under the oxycodone and noroxycodone concentration-time curve (AUC) values were comparable among the four groups. Compared with oxycodone, the oxymorphone AUC values were small, with significant differences between subject groups. AUC values were also calculated for the pharmacodynamic variable "drug effect," scored on a 100 mm visual analog scale. The two groups with the highest oxycodone AUC values (young and elderly women) had the lowest oxymorphone AUC values and the greatest drug effect AUC values. The two groups with the lowest oxycodone AUC values (young and elderly men) had the highest oxymorphone AUC values and the lowest drug effect AUC values. These results support oxycodone, and not oxymorphone, as being primarily responsible for pharmacodynamic and analgesic effects.

Administration, Oral↗
PubMed1995

A bioequivalence study of oral controlled-release morphine using naltrexone blockade.

Twenty-three normal volunteers who received morphine sulphate (MS Contin) with naltrexone completed this randomized, analytically blinded, two-way crossover comparison of the bioavailability of one 200-mg oral controlled-release morphine sulfate tablet with two 100-mg MSC tablets. Morphine effects were blocked by three 100-mg doses of naltrexone. The first dose of naltrexone was given 24 hours before MSC dosing, followed by a second dose at the time of MSC dosing and a third dose 24 hours after MSC administration. Compared with two 100-mg MSC tablets, the 200-mg tablet was 96% bioavailable (90% confidence interval, 88.14-105.74%). The 90% confidence intervals for mean Cmax and AUC0-24 for one 200-mg MSC tablet were within +/- 20% of the Cmax and AUC0-24 of two 100-mg tablets, indicating the two dosage forms are bioequivalent. Single 200-mg doses of MSC given with the naltrexone blockade were generally well tolerated, and adverse effects were similar to those reported for naltrexone alone and for lower doses of morphine without naltrexone. Naltrexone proved safe and effective in blocking the effects of controlled-release morphine, permitting bioequivalence studies of a high dose of morphine in normal volunteers.

Administration, Oral↗
PubMed1995

Relative bioavailability of controlled-release oral morphine sulfate during naltrexone blockade.

The effect of naltrexone hydrochloride on the bioavailability of 60 mg controlled-release oral morphine sulfate in normal volunteers was determined using a randomized, 2-way crossover, analytically blinded study design. Although naltrexone did not qualitatively alter the concentration-time curve for controlled-release morphine, the area under the plasma morphine concentration-time curve from 0-24 h (AUC0-24) was significantly greater (p < 0.01) for morphine given with naltrexone (265 ng x h/ml) than for morphine given alone (215 ng x h/ml). Compared to morphine given alone, the apparent absorption half-life of morphine was decreased from 0.94-0.58 h (p = 0.01) and Cmax was increased from 28.17 ng/ml to 32.26 ng/ml (p = 0.04) during naltrexone blockade, whereas the Tmax and apparent elimination half-life of morphine were not significantly affected. The minimal differences in morphine bioavailability indicate naltrexone may be useful in comparative bioavailability studies of high-dose opioids in opioid-naive normal volunteers.

Adult↗
PubMed1993

Analgesic efficacy and potency of two oral controlled-release morphine preparations.

MS Contin tablets and Oramorph SR tablets are two forms of oral controlled-release morphine sulfate available for the alleviation of pain. Our objective was to compare their analgesic effects in a relative potency assay. In this study, 151 patients undergoing caesarean section or abdominal hysterectomy and reporting moderate or severe postoperative pain received a 30 or 90 mg dose of either drug in a balanced, randomized, double-blind, parallel-group, single-dose experimental design. Patients provided self-ratings of analgesia. Relative potency for pain relief were calculated from log dose-effect curves. For total pain relief (rated by visual analog scales) over 12 hours, the log dose relative potency estimate for MS Contin tablets/Oramorph SR tablets was 1.9 (95% confidence limits, 0.89 to 11.1); for peak pain relief (visual analog scales) the relative potency estimate was 1.7 (95% confidence limits, 0.65 to 48.3). Overall, the 90 mg dose of MS Contin was more effective than 30 or 90 mg doses of Oramorph SR and the 30 mg dose of MS Contin at hours 6 to 12. Adverse experiences (mainly drowsiness) were mostly mild to moderate, with no significant differences in their overall incidence or severity between equivalent doses. MS Contin tablets provided greater peak, total, and duration of analgesia, without higher incidence of adverse experiences.

Administration, Oral↗
PubMed1993

In vitro efficacy of povidone-iodine solution and cream against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged worldwide as a significant and difficult-to-treat source of nosocomial infection, emphasizing the ever-present need for reliable and effective antisepsis. Betadine Solution (10% povidone-iodine; PVP-I) and Betadine Cream (5% povidone-iodine) are broad-spectrum microbicides widely used for topical cleansing, wound treatment, and antisepsis. There have been no reports of bacterial resistance to Betadine preparations. In the present study in vitro killing times were determined for PVP-I solution and PVP-I cream against five hospital isolates of MRSA and one methicillin-sensitive strain (MSSA). Isolates were incubated for 24 hours in trypticase soy broth and 0.5 ml, containing 10(6)-10(7)/ml bacteria, was then removed and added to each test agent containing PVP-I. At intervals of 30 seconds, 1 min, 2 min, 3 min, 5 min, 10 min, and 15 min, 10 microliters aliquots were removed and added to 10 ml of culture broth containing 0.1% sodium thiosulphate, the neutralizing agent for PVP-I. After neutralization the samples were incubated for 48 hours and then observed for growth (turbidity) or its absence. PVP-I solution was effective against all isolates, killing each strain within 30 seconds. PVP-I cream killed four of the MRSA isolates within 30 seconds, and required a 2-3 minute killing time for one strain of MRSA and the strain of MSSA. These results are supported by four published in vitro studies which show that PVP-I is highly effective in killing MRSA. In addition, each study shows that PVP-I is more effective than chlorhexidine against MRSA.

Humans↗
PubMed1993

An appraisal of povidone-iodine and wound healing.

Infection is one of the most frequent complications of wound healing despite the use of antibiotics and modern sterile technique; it accounts for considerable patient morbidity, discomfort, and prolonged hospitalization, and it must be avoided to permit proper healing. For this purpose, topical antiseptics have been employed for several years. Among these povidone-iodine formulations (polyvinylpyrrolidone iodine; PVP-I; e.g., Betadine preparations), which consist of a water-soluble complex of elemental iodine and a synthetic polymer, have a broad antimicrobial spectrum, and have not been reported to develop bacterial resistance. Because some reports have suggested that PVP-I may interfere with wound healing, a critical review of studies concerning PVP-I and wound healing was undertaken, with emphasis placed on in vivo models that replicate, as closely as possible, human wound healing. Four forms of PVP-I were evaluated: PVP-I solution, PVP-I skin cleanser/surgical scrub, PVP-I ointment, and PVP-I cream. PVP-I solutions had virtually no deleterious effect on wound healing: application of 10% PVP-I solution to rat, guinea pig, rabbit, or pig wounds did not reduce wound tensile strength or delay re-epithelialization. In three human studies, no significant difference in healing was observed for 1%, 5% or 10% PVP-I solution except for a slight delay during the first 24 hours after the application of 5% PVP-I solution in one study; healing was normal by 72 hours. PVP-I skin cleansers/surgical scrubs contain ammonium nonoxynol-4-sulphate and lauramide DEA which, like all detergents, can cause tissue damage and delay healing. This was substantiated by a guinea pig study in which the detergent component but no the antiseptic produced these effects. In human trials, no damage occurred if cleansing of the wound with PVP-I skin cleansers/surgical scrubs was followed by saline irrigation. These results are consistent with recommendations for promptly rinsing the wound with water to remove the detergent if detergent-containing PVP-I preparations are used for wound care. PVP-I ointment (10%) delayed wound closure inn rats during the fourth through tenth days post-treatment; however, during the next two weeks, healing was accelerated, and by day 24, healing was equal to the controls. No delays occurred when pigs or rabbits were tested. In human wounds, no delays occurred in healing, even when gel-type occlusive dressings were added to the wounds; in fact, bandage-wearing time was shortened in those patients treated with PVP-I ointment. PVP-I cream (5%) was also studied in humans; the cream formulation appeared to decrease healing time. Based on these studies, it can be concluded that povidone-iodine preparations do not have a deleterious effect on wound healing.

Animals↗
PubMed1992

The bioavailability of morphine in controlled-release 30-mg tablets per rectum compared with immediate-release 30-mg rectal suppositories and controlled-release 30-mg oral tablets.

The bioavailability of controlled-release morphine 30-mg tablets (MSC) administered orally or rectally and immediate-release morphine (RMS) 30-mg suppositories per rectum, was compared in this 14-subject, randomized, single-dose, analytically blinded, crossover study. Rectal MSC plasma morphine area under the curve from 0-24 hours (AUC0-24) was 50.8% of RMS and was similar for MSC administered by either route (rectal MSC = 90% oral MSC). Rectal MSC had a significantly delayed time to peak plasma level (5.4 vs 1.07 and 2.5 hrs for rectal MSC vs RMS and oral MSC, respectively) and a significantly attenuated time to maximum concentration (6.1 vs 25.4 and 9.7 ng/ml, respectively). Proctoscopy 24 hours after insertion revealed seven instances of mild, transient mucosal erythema or edema with rectal MSC and 12 with RMS. The number of nonlocal adverse effects was 14 with rectal MSC, 19 with RMS, and 18 with oral MSC. Further studies must determine the therapeutic consequences of pharmacokinetic differences and establish guidelines for rectal MSC use. The product is currently not recommended by the manufacturer for rectal administration.

Administration, Oral↗
PubMed1991

Chronotherapy of reversible airways disease with once-daily evening doses of a controlled-release theophylline preparation.

1. Asthma and COPD worsen at night and in the early morning, due to various circadian influences. 2. Uninterrupted sleep, stable lung function over 24 h, and reduced and stable airways responsiveness are primary therapeutic goals in asthma and COPD. 3. Once-daily evening theophylline chronotherapy meets these goals, providing rising blood levels at night and in the early morning, when most needed. 4. This regimen is now indicated for morning and evening dosing for reversible airway obstruction, in the United States and Canada, and marks the first available treatment for these diseases to include dosing time in the therapeutic strategy. It reflects increasing recognition by the medical community of the need to consider the individual patient's timing of symptoms in relation to the kinetics of the drug. 5. Theophylline chronotherapy is as well tolerated as more frequently administered methylxanthine preparations despite the relatively large single doses required by the prolonged dosing interval. The convenience of once-daily administration favors drug-taking compliance. 6. Theophylline chronotherapy does not provide constant blood levels over the 24-h day. Indeed, by improving lung function by means of a larger peak-to-trough difference than associated with twice-daily theophylline, once-daily chronotherapy has altered our thinking about theophylline pharmacodynamics.

Asthma↗
PubMed1990

A multi-investigator clinical evaluation of oral controlled-release morphine (MS Contin tablets) administered to cancer patients.

The analgesic efficacy of oral controlled-release morphine (MS Contin Tablets; MSC) and its influence on quality of life, including parameters of nighttime sleep and daytime functioning, were evaluated in this open-label, sequential study in cancer patients. Seventy patients completed this multi-investigator study; each patient was assigned to one of two dosing protocols, as determined by their previous analgesic regimen. Evaluations were made at baseline (when patients were receiving their previous analgesic regimen) and again on the second visit, after a dosage level of MSC sufficient to control pain was reached for a minimum of two weeks. There were no significant (p greater than 0.17) differences in incidence of nausea, vomiting, or drowsiness experienced by patients during treatment with MSC and during previous analgesic regimens. A senna and docusate sodium preparation (Senokot-S Tablets; SKS) was used to alleviate opioid-induced constipation; consequently there was a significantly lower (p = 0.02) incidence of constipation during treatment with MSC. A moderate relationship between opioid dose and laxative consumption was observed. Pain intensity was significantly (p = 0.0001) decreased, and quality of nighttime sleep and daytime functioning were significantly (p = 0.0001) increased compared with baseline values. Patients' overall quality of life improved significantly (p = 0.0001) during treatment with MSC when compared to their previous analgesic regimens. In conclusion, the therapeutic merits afforded by MSC coupled with proper dose titration were perceived by the patients to be superior to those provided by their previous medications. The benefits of less frequent dosing combined with potent analgesic effect plus the aggressive use of laxatives resulted in a global improvement in quality of life for the patients involved in this study.

Administration, Oral↗
PubMed1989

The United States experience with oral controlled-release morphine (MS Contin tablets). Parts I and II. Review of nine dose titration studies and clinical pharmacology of 15-mg, 30-mg, 60-mg, and 100-mg tablet strengths in normal subjects.

The results of nine US multicenter, sequential crossover, dose titration studies of controlled-release oral morphine (MS Contin 30 mg tablets [MSC], Purdue Frederick, Norwalk, CT) are reviewed in Part I. The studies demonstrated the prolonged analgesic efficacy of the preparation in the treatment of patients with moderate to severe cancer-related pain. Approximately 93% of the patients achieved satisfactory to excellent analgesia on a 12-hour regimen when appropriate dose titration was allowed. The remaining patients were successfully maintained on an 8-hour regimen. The preparation was well-tolerated and comparable in safety to immediate-release oral morphine. In global evaluations, MSC was judged to be significantly (P less than 0.05) more effective, and with significantly (P less than 0.05) fewer side effects than both the prestudy opioid analgesics and 4-hour immediate-release oral morphine. Patients had a broad range of morphine requirements (mean daily MSC dose, 240 mg; range, 60 mg/day to 1800 mg/day); therefore various MSC tablet strengths were developed. Part II presents three studies in which the MSC formulations (15-mg, 60-mg, and 100-mg tablets) were compared to the 30-mg tablet within three randomized, single-dose, two-way crossover, analytically blinded bioavailability protocols, to determine bioequivalence and dose proportionality. The maximum morphine concentration, time of maximum morphine concentration, and area under the plasma morphine versus 12-hour and 24-hour time curve (AUC 0.12; AUC 0.24) were determined in each study. There were no significant differences between the values associated with MSC 1 X 30 mg tablet and 2 X 15 mg tablets (study 1), MSC 2 X 30 mg tablets and 1 X 60 mg tablet (study 2), and MSC 3 X 30 mg tablets and 1 X 100 mg tablet (study 3, values adjusted to dose of 90 mg), except for one marginally significant difference in study 3 (AUC 0.24; P = 0.04) which was not clinically or biopharmaceutically significant. The results showed that MSC 15-mg, 30-mg, 60-mg, and 100-mg dosage strengths are bioequivalent and dose proportional, and, therefore, therapeutically interchangeable. It was concluded that with routine assessment of the patient and adherence to the principles of analgesic dosing, MSC can be successfully used to control cancer-related pain. Furthermore, the availability of various MSC tablet strengths can be expected to facilitate the analgesic management of a patient population with widely differing opioid requirements.

Administration, Oral↗
PubMed1989

Circadian variations in theophylline concentrations and the treatment of nocturnal asthma.

The nocturnal worsening of asthma is a common problem that can be difficult to treat. Two different sustained-release theophylline preparations were used to determine (1) if the serum theophylline concentrations (STC) depend on the type and dosing schedule of the preparation, (2) the relationship between STC and the circadian variations in asthma, and (3) the effect of STC on sleep quality and respiratory patterns during the night. In 16 subjects with nocturnal asthma, the STC were significantly higher during the daytime on twice-daily versus once-daily theophylline preparations given at 7 P.M., but the FEV1 values were similar. During the night, the STC were significantly higher with the once-daily regimen, and the awakening FEV1 value was also improved (p less than 0.05). All polysomnographic variables were similar between the two preparations, except that with the once-daily preparation there was a decreased number of hypopneas (p less than 0.05) and fewer minutes below an oxygen saturation of 90% (p less than 0.05). We conclude that patients with nocturnal asthma need their treatment focused on the nocturnal portion of the circadian cycle and that higher STC during this critical time period are beneficial without interfering with sleep quality.

Adult↗