Biomedical subjects

C Nora Chiang

Publications and source records attributed to C Nora Chiang.

6 recordsLinked to original sources

PubMed2006

Methylphenidate and cocaine: a placebo-controlled drug interaction study.

Up to thirty percent of cocaine addicted individuals may meet diagnostic criteria for Attention-Deficit/Hyperactivity Disorder (ADHD). Methylphenidate (MPH) is a highly effective and commonly used treatment for ADHD but, like cocaine, is a cardiovascular and central nervous system stimulant with the potential to cause toxicity at high doses. The present study was undertaken to investigate the likelihood of a toxic reaction in individuals who use cocaine while concurrently taking MPH. Seven non-treatment seeking cocaine-dependent individuals completed this placebo-controlled, crossover study with two factors: Medication (placebo, 60 mg MPH, 90 mg MPH) and Infusion (saline, 20 mg cocaine, 40 mg cocaine). Physiological measures included vital signs, adverse events, and electrocardiogram. Subjective response was measured with visual analog scale (VAS) ratings of craving and drug effect. Cocaine pharmacokinetic parameters were calculated for each participant at each drug combination, using a non-compartmental model. MPH was well tolerated, did not have a clinically significant impact on cocaine's physiological effects, and decreased some of the positive subjective effects of cocaine. MPH did not significantly alter the pharmacokinetics of cocaine. The study results suggest that MPH at the doses studied can likely be used safely in an outpatient setting with active cocaine users.

Adult↗

PubMed2006

Intravenous cocaine and QT variability.

BACKGROUND: Dynamic instability in cardiac repolarization may contribute to drug-induced arrhythmogenesis. We hypothesized that intravenous cocaine would significantly destabilize repolarization as measured by QT variability. METHODS AND RESULTS: Twenty-nine cocaine-experienced volunteers not seeking treatment for cocaine addiction received randomized, sequential intravenous infusions of placebo or cocaine (20 and 40 mg). Five-minute epochs of digitized ECG were recorded 10 minutes before, during, and at intervals following the infusions. QT variability was measured using a semiautomated method and expressed as the log ratio of normalized QT variance to normalized heart rate variance (QTVI). Seventeen subjects received a repeat course of cocaine infusions 1 week later. Placebo infusion resulted in a small but significant increase in QTVI, while cocaine caused a highly significant, dose-dependent increase in QTVI that peaked at 10 minutes and dissipated by 45 minutes following infusion (P < 0.0001). The increase in QTVI was reproducible at 1 week (P = 0.8). CONCLUSIONS: Cocaine injection results in a significant dose-dependent increase in QT variability as indexed by QTVI. This destabilizing effect on repolarization may increase vulnerability to reentrant arrhythmias and may partially explain an increased risk of sudden cardiac death associated with cocaine use.

Adult↗

PubMed2006

Pharmacokinetics and pharmacodynamics of multiple sublingual buprenorphine tablets in dose-escalation trials.

In this investigation, the pharmacokinetic and pharmacodynamic properties were determined of multiple doses of sublingual tablets containing either buprenorphine alone or buprenorphine and naloxone. Subjects were experienced opiate users who received escalating doses (4-24 mg) of buprenorphine either alone or in combination with naloxone. Peak concentration (Cmax) and area under the concentration-time curves (AUCs) increased for both buprenorphine and naloxone with escalating doses. Significant differences were found across the range of doses administered for dose-adjusted Cmax for both tablet formulations and for the dose-adjusted AUCs for the buprenorphine-naloxone tablets. For both formulations, the maximal buprenorphine-induced decreases in respiratory rate and pupil diameter did not vary significantly across doses. Several of the subjective effects of buprenorphine did not increase as the dose of buprenorphine administered was increased. These findings are consistent with the ceiling effect associated with the partial agonist actions of buprenorphine. They also indicate a lack of dose proportionality for buprenorphine sublingual tablets, at least during the times at which levels of this agent are highest.

Administration, Sublingual↗

PubMed2005

Modafinil influences the pharmacokinetics of intravenous cocaine in healthy cocaine-dependent volunteers.

OBJECTIVE: To determine if modafinil, a putative treatment for cocaine dependence, influences the pharmacokinetics of intravenous cocaine in otherwise healthy cocaine-dependent volunteers. METHODS: Cocaine 20 or 40 mg was administered intravenously on consecutive days over 1 minute at baseline and after modafinil administration at each of two dosages of 400 and 800 mg/day for 7 days. RESULTS: Twelve subjects completed the clinical protocol. Compared with baseline, the cocaine peak plasma concentration was decreased after both the 20 and 40 mg cocaine infusions, but the reduction was only statistically significant after the 40 mg cocaine infusion (p < 0.01 after modafinil 400 mg/day; p < 0.05 after modafinil 800 mg/day). The area under the cocaine plasma concentration-time curve from 0 to 180 minutes (AUC180) was significantly decreased by modafinil administration (p < 0.01 and p < 0.001 for modafinil 400 and 800 mg/day, respectively, for the cocaine 20mg dose; p < 0.001 for the cocaine 40 mg dose at both modafinil levels). There were no significant changes in total AUC, clearance or elimination half-life of cocaine. CONCLUSION: This study did not find evidence for a harmful pharmacokinetic interaction between modafinil and cocaine. In contrast, long-term administration of modafinil significantly decreased systemic exposure to cocaine during the first 180 minutes following intravenous cocaine administration.

Administration, Oral↗

PubMed2003

Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone.

BACKGROUND: Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone has been proposed, but its efficacy and safety have not been well studied. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving 326 opiate-addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine (16 mg) in combination with naloxone (4 mg), buprenorphine alone (16 mg), or placebo given daily for four weeks. The primary outcome measures were the percentage of urine samples negative for opiates and the subjects' self-reported craving for opiates. Safety data were obtained on 461 opiate-addicted persons who participated in an open-label study of buprenorphine and naloxone (at daily doses of up to 24 mg and 6 mg, respectively) and another 11 persons who received this combination only during the trial. RESULTS: The double-blind trial was terminated early because buprenorphine and naloxone in combination and buprenorphine alone were found to have greater efficacy than placebo. The proportion of urine samples that were negative for opiates was greater in the combined-treatment and buprenorphine groups (17.8 percent and 20.7 percent, respectively) than in the placebo group (5.8 percent, P<0.001 for both comparisons); the active-treatment groups also reported less opiate craving (P<0.001 for both comparisons with placebo). Rates of adverse events were similar in the active-treatment and placebo groups. During the open-label phase, the percentage of urine samples negative for opiates ranged from 35.2 percent to 67.4 percent. Results from the open-label follow-up study indicated that the combined treatment was safe and well tolerated. CONCLUSIONS: Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting.

Administration, Sublingual↗

PubMed2003

Pharmacokinetics of the combination tablet of buprenorphine and naloxone.

The sublingual combination tablet formulation of buprenorphine and naloxone at a fixed dose ratio of 4:1 has been shown to be as effective as the tablet formulation containing only buprenorphine in treating opiate addiction. The addition of naloxone does not affect the efficacy of buprenorphine for two reasons: (1) naloxone is poorly absorbed sublingually relative to buprenorphine and (2) the half-life for buprenorphine is much longer than for naloxone (32 vs. 1 h for naloxone). The sublingual absorption of buprenorphine is rapid and the peak plasma concentration occurs 1 h after dosing. The plasma levels for naloxone are much lower and decline much more rapidly than those for buprenorphine. Increasing dose results in increasing plasma levels of buprenorphine, although this increase is not directly dose-proportional. There is a large inter-subject variability in plasma buprenorphine levels. Due to the large individual variability in opiate dependence level and the large variability in the pharmacokinetics (PK) of buprenorphine, the effective dose or effective plasma concentration is also quite variable. Doses must be titrated to a clinically effective level for individual patients.

Administration, Sublingual↗