An epidemiologic postmarketing surveillance study of prescription acne medications.

After the Food and Drug Administration approved a topical antibiotic for the treatment of acne, we began a postmarketing surveillance study to measure the frequency of antibiotic-associated colitis and diarrhea in acne patients treated with topical antibiotics and low doses of oral antibiotics. Pharmacists recruited 13,465 patients who presented a prescription for an acne medication, and we obtained detailed information on the use of the medications, perceived acceptability, and the occurrence of new health events from 6,453 with computer-assisted telephone interviews. Three cases (less than 0.1%) of antibiotic-associated diarrhea and one case (less than 0.1%) of antibiotic-associated colitis were confirmed. We conclude that this methodology can provide further information about the safety of a drug once it is in customary use, at a fraction of the cost of Phase III clinical trials.

Cyclazocine-induced sleep disruptions in nondependent addicts.

After one adaptation night, the sleep of seven male nondependent opiate addicts was studied following intramuscular cyclazocine (0.125; 0.25; 0.50 mg/70 kg) or placebo at weekly intervals in a randomized double-blind crossover design. Drug effects were measured on sleep stages and several episodic phenomena. Cyclazocine caused dose-related increases in sleep latency, REMS latency, percent spindle sleep, and a marked increase over placebo in wakefulness, drowsiness, and shifts in sleep-waking states. Cyclazocine produced a dose-related decrease in all measures of delta sleep, and some measures of REMS, and a marked decrease below placebo of sleep efficiency and total REMS. All doses of cyclazocine caused sustained periods of waking with little muscle tension. Cyclazocine (0.5mg) consistently caused urination during periods of extended arousal; urination has not been seen after morphine or other opioids of the mu type. These studies indicate that cyclazocine has effects on human sleep which are in some ways similar and other ways dissimilar to morphine type analgesics. The results are consistent with the concept that cyclazocine is a mixed agonist-antagonist of the opioid type with agonist actions at the kappa receptor.

A comparison of Cleocin T 1 percent solution and Cleocin T 1 percent lotion in the treatment of acne vulgaris.

A randomized, investigator-blind study was conducted to compare the efficacy and skin tolerance of Cleocin T Topical 1 percent Solution and Cleocin T Topical 1 percent Lotion. Both treatments reduced acne lesion counts. More than 70 percent of the evaluable patients receiving each treatment reported that their acne improved by the end of the twelve-week study. Skin dryness was reported significantly more often by patients applying the solution than by those applying the lotion. This newly developed lotion formulation of topical clindamycin phosphate is equal in efficacy to, and appears to be less irritating than, Cleocin T Topical Solution.

Morphinelike arousal by methadone during sleep.

Methadone was investigated to see if it induced an insomnia comparable to that after single doses of morphine. After one adaptation night, the sleep of seven male nondependent opiate addicts was studied after intramuscular methadone (7.5, 15, or 30 mg/70 kg), morphine (10 or 20 mg/70 kg), and placebo at weekly intervals in a randomized double-blind crossover design. Drug effects were measured on several sleep and wakefulness patterns. Methadone is equipotent to morphine in its increase of wakefulness, drowsiness, muscle tension, shifts in sleep-waking state, and latency to rapid eye movement sleep (REMS) and its decrease of sleep efficiency, delta sleep, and REMS. This similarity of methadone to morphine in acute arousal from sleep is in contrast to the differences between these two drugs during long-term administration, when morphine induces a small but persistent arousal and methadone does not.

Defeated and joyless: potential measures of change in drug abuse characteristics.

Defeated and Joyless scales were developed from a questionnaire given to 54 normal, 53 alcoholic, and 28 opiate addict subjects. The Defeated scale differentiates the alcoholics and addicts from normals but not from each other, whereas the Joyless scale differentiates addicts from both alcoholics and normals. When shown to 48 college students, a film about poverty increased the Joyless score, as well as other measures, but had little effect on the Defeated score. These scales appear to distinguish between self-concept (Defeated) and mood (Joyless) components of hypophoria, an affective disorder hypothesized to be associated with drug abuse.

Psychopathic State Inventory (PSI): development of a short test for measuring psychopathic states.

Six rational psychopathic state scales for Impulsivity, Egocentricity, Needs, Hypophoria (negative feeling states), Sociopathy, and High (search for "highs") were revised by selecting items within a rational category which most highly differentiated psychopaths as exemplified by opiate addicts (N = 28) and alcoholics (N = 53) from normals (N = 54) and which also most highly correlated with the parent rational scale or correlated most highly with the differentiating items. These procedures were effective in deriving scales which more highly differentiated alcoholics and addicts from normals and which were more reliable in each criterion group. It is thought that the scales will be useful in the study of the prevalence of or changes in psychopathic states.

Opioid effects on computer-derived sleep and EEG parameters in nondependent human addicts.

After one adaptation night, intramuscular doses of methadone (7.5, 15, 30 mg/70 kg), morphine (10 or 20 mg/70 kg), or placebo were given to seven male nondependent opiate addicts at weekly intervals in a randomized cross-over design. After three adaptation nights, heroin (3, 6, 12 mg/70 kg) was compared with morphine and placebo by means of a similar design in seven other subjects. Using electroencephalogram (EEG) bisector analysis, tape recordings of sleep were analyzed for two beta, three alpha, three theta, and two delta EEG patterns, as well as for detections of sleep spindles, K-complexes, eye movements, body movements, average electromyogram (EMG), and calculation of seven sleep-waking stages. All three opioids produce a dose-related arousal: they increase EMG and EEG measures of muscle activity, as well as body movements and EEG alpha, while decreasing EEG theta and spindling. These opioids also increase measures of waking state and decrease measures of spindle sleep and REM sleep. Although the 1974 version of the EEG bisector analysis is not exactly comparable to visual analysis, in this design it defined significant drug effects on sleep and EEG. Distinctive bisector analysis patterns are positively correlated with each sleep--waking stage.

Concentrations of phenethylamine in dog following single doses and during intravenous self-administration.

A gas chromatographic procedure is described which was used to measure concentrations of beta-phenethylamine (PEA) in dog plasma following single or multiple infusions. Plasma levels were determined immediately following drug infusions during PEA self-administration sessions. At a unit dose of 3 mg/kg/infusion the concentration of PEA ranged from 1 to 3.95 microgram/ml of plasma, and from 2.5 to 4.75 microgram/ml at a unit dose of 6 mg/kg/infusion. At the time of responding for another infusion the plasma concentration varied between 0.16 and 0.52 microgram/ml and between 0.08 and 0.26 microgram/ml, for the two doses, respectively. Whole-body concentrations of PEA during self-administration were estimated according to a one compartment, open model using experimentally determined plasma half-lives obtained from single dose studies and inter-infusion intervals. Relatively little accumulation of PEA was predicted according to this model which correlated well with the experimental data. During the course of a self-administration session plasma levels rose initially following the infusion and declined to relatively constant levels ("response concentrations") when a subsequent drug-seeking response was made. Significant differences in "response concentrations" were observed between dogs and between doses. It is suggested that this response pattern is related to the distribution and clearance rate of the drug from plasma and well-perfused tissues.