联苯双酯

本品含磷酸苯丙哌林(C₂₁H₂₇NO·H₃PO₄)应为标示量的90.0~110.0%。     

磷酸苯丙哌林片

本品含磷酸苯丙哌林(C₂₁H₂₇NO·H₃PO₄)应为标示量的90.0~110.0%。     

盐酸多塞平片

本品含盐酸多塞平按多塞平(C₁₉H₂₁NO)计算应为标示量的90~110.0%。     

盐酸多塞平注射液

本品为盐酸多塞平的灭菌水溶液,含量按多塞平计算(C₁₉H₂₁NO)应为标示量的90.0~110.0%。     

国家食品药品监督管理局国家药品标准修订——谷红注射液

本品为乙酰谷酰胺与红花提取液混合制成的灭菌水溶液。本品每1 mL中含乙酰谷酰胺(C₇H₁₂N₂O₄)应为27 mg~33 mg;含红花以羟基红花黄色素A(C₂₇H₃₂O₁₆)计,不得少于0.15 mg。     

中国乌头的研究 Ⅷ.黄草乌根中的生物碱

从云南黄草乌根中分得三种生物碱,其中两种暂称为黄草乌碱甲及乙.甲碱C₃₃H₄₇O₉N,熔点为182-184℃;乙碱C₂₁H₃₃O₄N,熔点为184-185℃;和另一微量生物碱,熔点151-152℃.其中甲碱为主要成分,经官能团测定后,定其示性式为C₁₉H₂₁(OH)₂(OCH₃)₄-(CH₃OC₆H₄COO)(N-C₂H₅).     

盐酸羟嗪片

本品含盐酸羟嗪(C₂₁H₂₇C₁N₂O₂·₂HCl)应为标示量的93.0~107.0%。     

磷酸苯丙哌林

本品为l-[2-(2-苄基苯氧基)-1-甲基乙基]哌啶磷酸盐,按干燥品计算,含C₂₁H₂₇NO·H₃PO₄不得少于98.5%。[性状]本品为白色或几乎白色粉末;微带特臭,味苦。本品在水中易溶,在乙醇、氯仿或苯中略溶,在丙酮或乙醚中不溶。     

盐酸普罗帕酮胶囊

本品含盐酸普罗帕酮(C₂₁H₂₇NO₃·Hcl)应为标示量的90.0~110.0%。     

中国乌头的研究——Ⅹ.关白附子中的新生物碱

从关白附子(Aconitum koreanum R.Raymund)中共分得六种生物碱。其中一种是已知生物碱,卽次乌头碱,另五种为新生物碱,暂称为关附甲素C₂₄H₃₁O₆N、乙素C₂₂H₂₉O₅N、丙素C₂₂H₃₃O₂N、丁素C₂₄H₃₅O₃N及戊素C₂₉H_(43)O₇N。关附甲素是关附乙素的一乙酸酮。关附甲素、乙素、丙素的示性式分别定为:C₁₉H₂₀(OH)₂(CH₃COO)₂(CH₃)(∶N·),C₁₉H₂₀(OH)₃(CH₃COO)(CH₃)(∶N·),C₁₉H₂₃(OH)₂(CH₃)(N—C₂H₅)。后二种生物碱因量少尚待研究。     

Electrocardiogram characteristics of methadone and buprenorphine maintained subjects

There has been recent concern about the association between high dose methadone and prolongation of QTc in the electrocardiogram. QTc is the time from the beginning of the QRS complex to the end of the T have as measured on an electrocardiogram and corrected for heart rate. To date, no association has been made between methadone and buprenorphine in commonly used doses and prolonged QTc. Electrocardiograms were performed on groups of methadone (n = 35, mean daily dose +/- standard deviation, 69 +/- 29 mg) and buprenorphine (n = 19, mean daily dose 11 +/- 5 mg) subjects and a group of non-opioid dependent controls (n = 17). Mean QTc did not differ (p = 0.45) between methadone, buprenorphine, or controls. Methadone subjects were significantly (odds ratio of 7.8) more likely to have U waves than buprenorphine and controls combined. Methadone subjects with U waves were maintained on higher (p = 0.004) doses (89 +/- 29 mg/day) than methadone subjects without U waves (60 +/- 24 mg/day). Methadone subjects taking 60 mg and above had higher (p = 0.02) QTc (405 +/- 29 milliseconds) than methadone subjects taking less than 60 mg per day (381 +/- 27 milliseconds). Although an association is thought to exist between high methadone doses and elongated QTc, methadone and buprenorphine, at commonly used daily doses, remain safe agents for opioid substitution therapy.     

Electrocardiogram Characteristics of Methadone and Buprenorphine Maintained Subjects

ABSTRACT

There has been recent concern about the association between high dose methadone and prolongation of QTc in the electrocardiogram. QTc is the time from the beginning of the QRS complex to the end of the T have as measured on an electrocardiogram and corrected for heart rate. To date, no association has been made between methadone and buprenorphine in commonly used doses and prolonged QTc. Electrocardiograms were performed on groups of methadone (n = 35, mean daily dose ± standard deviation, 69 ± 29 mg) and buprenorphine (n = 19, mean daily dose 11 ± 5 mg) subjects and a group of non-opioid dependent controls (n = 17). Mean QTc did not differ (p = 0.45) between methadone, buprenorphine, or controls. Methadone subjects were significantly (odds ratio of 7.8) more likely to have U waves than buprenorphine and controls combined. Methadone subjects with U waves were maintained on higher (p = 0.004) doses (89 ± 29 mg/day) than methadone subjects without U waves (60 ± 24 mg/day). Methadone subjects taking 60 mg and above had higher (p = 0.02) QTc (405 ± 29 milliseconds) than methadone subjects taking less than 60 mg per day (381 ± 27 milliseconds). Although an association is thought to exist between high methadone doses and elongated QTc, methadone and buprenorphine, at commonly used daily doses, remain safe agents for opioid substitution therapy.     

Methadone versus buprenorphine maintenance for the treatment of heroin-dependent outpatients

The aim of this study was to assess the efficacy of methadone compared with buprenorphine maintenance therapy in heroin-dependent patients over a treatment period of 18 weeks. Subjects were randomized to receive either methadone or buprenorphine in a comparative double-blind study and consisted of 164 heroin-dependent male patients who met the DSM-IV criteria for heroin dependence and were seeking treatment. The 164 subjects included 41 patients in 1-mg, 41 patients in 3-mg, and 41 patients in 8-mg dosage group of buprenorphine, and also 41 patients in the 30-mg dosage group of methadone. The mean age was 31.4 years for total buprenorphine group and 33.7 years for methadone group (the mean age differences in 4 groups were not statistically significant). Subjects received buprenorphine at a dose of 1, 3, or 8 mg per day or methadone at a dose of 30 mg per day and were treated in an urban outpatient clinic, offering a 1-hour weekly individual counseling session. Days retained in treatment were measured. Completion rates by buprenorphine dosage group were 29.3% for the 1-mg dose group, 46.3% for the 3-mg dose group, 68.3% for the 8-mg dose group, and 61% for the 30-mg methadone dose group. Retention in the 8-mg dose group was significantly better than in the 1-mg dose group (p=.00041) and in the 3-mg dose group (p=.045); other comparison (1 mg dose with 3 mg dose) was not significant. Methadone group was significantly better than 1mg buprenorphine dose group (p=.004), but was not significantly different from 3 mg buprenorphine dose group (p=.18) or 8 mg buprenorphine dose group (p=.49). The results support the efficacy of buprenorphine for outpatient treatment of heroin dependence and seem to indicate that the highest dose (8 mg) of buprenorphine was the best of the three doses of buprenorphine, and also support the superiority of 30 mg of methadone compared to 1 mg dose of buprenorphine for Iranian heroin-dependent patients to increase their retention in treatment.     

Effects of perinatal buprenorphine and methadone exposures on striatal cholinergic ontogeny

The effects of exposure to various doses of buprenorphine, methadone or water during the perinatal period were studied on striatal cholinergic development in the rat. Rats were exposed to buprenorphine (0.3 or 3.0 mg/kg/day), methadone (9 mg/kg/day) and/or water prenatally, postnatally or both pre- and postnatally via maternally implanted osmotic minipumps. The effects of buprenorphine varied with the dose used. There were some similarities between the effects of perinatal buprenorphine and perinatal methadone, such as a reduction in striatal acetylcholine (ACh) content in 4-day-old pups exposed prenatally to methadone or buprenorphine (0.3 mg/kg/day). However, differences were also observed between the effects of the two drugs. Unlike methadone, the 0.3-mg/kg/day dose of buprenorphine produced a sex-related increase in striatal ACh in male postnatal day (PND) 21 pups. The 3-mg/kg/day dose of buprenorphine produced a completely different range of results, such as decreased striatal ACh content in 4-day-old pups exposed to the drug postnatally and in 21-day-old pups exposed both pre- and postnatally. Differences in the effects of the two drugs may be related to the different affinities and efficacies of the drugs at different opioid receptor subtypes.     

Cessation of methadone maintenance treatment using buprenorphine: transfer from methadone to buprenorphine and subsequent buprenorphine reductions

BACKGROUND: Buprenorphine is used in the treatment of opioid dependence. Due to its pharmacology, the transfer from methadone to buprenorphine may precipitate withdrawal symptoms. METHODS: Methadone maintained patients with clinical indicators of stability who were seeking withdrawal from methadone were recruited from three Australian states. Patients on methadone doses between 30 and 40 mg were randomised to transfer to buprenorphine by a fixed dose (transfer at 30 mg methadone) or by a variable dose induction (transfer when 'uncomfortable'). A third group of patients with methadone doses less than 30 mg were transferred to buprenorphine at their entry methadone dose. Fifty-one patients were inducted onto buprenorphine using the same dosing protocol with the first dose of 4 mg buprenorphine. Following stabilisation on buprenorphine, patients gradually reduced the buprenorphine dose to 0 mg. Withdrawal severity and drug use was monitored. RESULTS: There were no significant difference between the transfer at 30 mg and transfer when 'uncomfortable' dosing protocols in severity of withdrawal on transfer from methadone to buprenorphine. Those on doses less than 30 mg reported significantly less withdrawal discomfort at transfer. All but one patient stabilised on buprenorphine. Thirty-eight of the 51 patients inducted onto buprenorphine reached 0 mg. CONCLUSIONS: Transfer from methadone to buprenorphine can safely occur from doses of around 30 mg of methadone. Buprenorphine dose reductions were well tolerated. Thirty-one percent of patients were not using heroin or methadone at 1-month follow-up.     

Effects of buprenorphine and methadone in methadone-maintained subjects

Buprenorphine, a partial mu opioid agonist, is an experimental medication under development for the treatment of opioid dependence as an alternative to methadone maintenance. The present study examined the relationship between level of opioid physical dependence and response to buprenorphine administration as part of a program to develop procedures for transferring patients from methadone to buprenorphine treatment. This laboratory study characterized the agonist and antagonist effects of acute doses of buprenorphine and methadone in subjects maintained on either 30 (n=7) or 60 (n=6) mg/day oral methadone. Test doses of placebo [sl. and PO), methadone (15, 30, and 60 mg PO) and buprenorphine (2, 4, and 8 mg sl.) were administered to volunteers residing on a closed residential unit. Subjective, physiological, observer-rated, and cognitive/psychomotor measures were collected for 6.5 h after test doses. Test doses of methadone, but not buprenorphine, constricted pupils and produced dose-related increases on subjective report measures reflecting opioid agonist drug effects. Agonist effects of methadone were more prominent in the 30 mg than in the 60 mg methadone maintenance condition. Buprenorphine, but not methadone, precipitated opioid withdrawal signs and symptoms that were more prominent in the 60 mg than in the 30 mg methadone maintenance condition. These findings suggest that abrupt transition from methadone to buprenorphine may produce patient discomfort that is positively related to both methadone maintenance dose and buprenorphine transition dose.     

Economic evaluation: A comparison of methadone versus buprenorphine for opiate substitution treatment

Background

The cost of opiate substitution is usually considered lower in cost when methadone is used, as compared to that of buprenorphine, however the overall cost effectiveness of substitution programmes comparing the two drugs remains largely unknown.

Methods

We evaluated the treatment cost and effectiveness of methadone and buprenorphine when used in an opiate substitution programme in Norfolk, UK. All programme costs, estimated from the perspective of the drug treatment clinic, were collected on 361 opiate-dependent participants over a six-month period. Total costs comprised medication (methadone or buprenorphine) costs, pharmacy supervision and dispensing costs, and drug service clinic costs. Effectiveness was measured in terms of (1) each programmes ability to retain participants in the programme for six months, and (2) the ability of the programme to accomplish complete abstinence from illicit opiate consumption.

Results

Overall, mean medication-only costs of methadone were lower than that of buprenorphine, however, pharmacy and clinic costs were lower for the buprenorphine programme. The covariate-adjusted mean total cost of the two programmes was not significantly different. Mean six-month retention rates were higher on the methadone programme, therefore, the methadone programme “dominates” the buprenorphine programme as it was slightly more effective for the same cost. Conversely, when ability to stop taking illicit opiates concomitant with opiate substitution medication was considered, the buprenorphine programme was more effective with an additional cost of £903 per individual who stopped illicit opiate use.

Conclusions

The provision of buprenorphine should be considered an appropriate treatment if cessation of illicit opiate use, concomitant with programme retention is considered an important outcome.     

The practice of office-based buprenorphine treatment of opioid dependence: is it associated with new patients entering into treatment?

Office-based buprenorphine holds the promise of bringing patients who have never received pharmacotherapy into treatment. In a cross-sectional and longitudinal analysis, we compared patients entering a clinical trial of buprenorphine in a Primary Care Clinic (PCC) and those entering a local Opioid Treatment Program (OTP) and we compared the clinical characteristics and treatment outcomes of PCC patients with no history of methadone treatment (new-to-treatment) to those with prior methadone treatment. PCC subjects (N=96) were enrolled in a 26-week randomized clinical trial of office-based buprenorphine/naloxone provided in a PCC. OTP subjects (N=94) were enrolled in methadone maintenance during the same time period. PCC subjects compared with OTP subjects were more likely to be male (77% versus 55%, p<0.01), full-time employed (46% versus 15%, p<0.001), have no history of methadone treatment (46% versus 61%, p<0.05), have fewer years of opioid dependence (10 versus 15, p<0.001), and lower rates of injection drug use (IDU) (44% versus 60%, p=0.03). The new-to-treatment PCC subjects were younger (36 years versus 41 years, p=0.001), more likely to be white (77% versus 57%, p=0.04), had fewer years of opioid dependence (7 versus 14, p<0.001), were less likely to have a history of IDU (35% versus 54%, p=0.07), and had lower rates of hepatitis C (25% versus 61%, p=0.002) than subjects with prior methadone treatment. Abstinence and treatment retention were comparable in both groups. The results suggest that office-based treatment of opioid dependence is associated with new types of patients entering into treatment. Treatment outcomes with buprenorphine in a PCC do not vary based on history of prior methadone treatment.     

Pilot randomised controlled trial of community pharmacy administration of buprenorphine versus methadone

Objectives The established regime for opiate substitute prescribing for drug misusers is daily methadone administered under supervision in community pharmacies. Buprenorphine has recently been introduced as an alternative. However there is a lack of evidence of the effectiveness of buprenorphine maintenance therapy (BMT) in the UK treatment setting. This study aimed to assess methods for a randomised controlled trial (RCT) and the feasibility of pharmacy‐based supervised self‐administration (SSA) of buprenorphine compared to methadone. Setting Specialist substance misuse service, general practices and community pharmacies in Aberdeen, Scotland. Method The design was a pilot RCT. Opiate‐dependent drug misusers, newly referred for maintenance treatment were randomised to receive BMT or methadone maintenance therapy (MMT). Clients and pharmacists were interviewed at baseline and at the end of a 12‐week intervention period. Clients completed the quality of life measure EQ‐5D. Pharmacy activities were timed. Key findings Twenty‐one opiate‐dependent clients were recruited (BMT = 11, MMT = 10). Recruitment levels improved as the trial progressed. Clients' treatment preferences were evident. Withdrawals occurred early with BMT. Clients found SSA of buprenorphine acceptable, but found daily administration more manageable than three times weekly. Pharmacists found the dispensing of buprenorphine to be an acceptable role, but felt less certain of ensuring against diversion with buprenorphine than they were with methadone. Pharmacy activities associated with buprenorphine took longer than those associated with methadone (mean = 7 min 25 s versus mean = 3 min 27 s, respectively). Conclusion Recruitment to a trial comparing MMT to BMT for opiate‐dependent clients within a UK treatment setting is feasible. Clients and pharmacists found buprenorphine acceptable.     

Methadone and buprenorphine-naloxone are effective in reducing illicit buprenorphine and other opioid use,and reducing HIV risk behavior—Outcomes of a randomized trial

Aims

Determine the extent to which buprenorphine injectors continue treatment with buprenorphine-naloxone or methadone, and the impact of these treatments on substance use and HIV risk in the Republic of Georgia.

Methods

Randomized controlled 12-week trial of daily-observed methadone or buprenorphine-naloxone followed by a dose taper, referral to ongoing treatment, and follow-up at week 20 at the Uranti Clinic in Tbilisi, Republic of Georgia. Eighty consenting treatment-seeking individuals (40/group) aged 25 and above who met ICD-10 criteria for opioid dependence with physiologic features and reported injecting buprenorphine 10 or more times in the past 30 days. Opioid use according to urine tests and self-reports, treatment retention, and HIV risk behavior as determined by the Risk Assessment Battery.

Results

Mean age of participants was 33.7 (SD5.7), 4 were female, mean history of opioid injection use was 5.8 years (SD4.6), none were HIV+ at intake or at the 12-week assessment and 73.4% were HCV+. Sixty-eight participants (85%) completed the 12-week medication phase (33 from methadone and 35 from buprenorphine/naloxone group); 37 (46%) were in treatment at the 20-week follow-up (21 from methadone and 16 from the buprenorphine/naloxone group). In both study arms, treatment resulted in a marked reduction in unprescribed buprenorphine, other opioid use, and HIV injecting risk behavior with no clinically significant differences between the two treatment arms.

Conclusions

Daily observed methadone or buprenorphine-naloxone are effective treatments for non-medical buprenorphine and other opioid use in the Republic of Georgia and likely to be useful for preventing HIV infection.