Buprenorphine Research Articles

Antinociceptive effects of intravenous administration of hydromorphone hydrochloride alone or followed by buprenorphine hydrochloride or butorphanol tartrate to healthy conscious cats.

To evaluate antinociceptive effects of IV administration of hydromorphone alone or followed by buprenorphine or butorphanol to cats. 6 healthy adult cats. In a randomized, blinded crossover design, cats received each of 4 treatments in which 2 IV injections were given 30 minutes apart: 2 of saline (0.9% NaCl) solution (Sal-Sal) or 1 each of hydromorphone HCl and saline solution (H-Sal), hydromorphone and buprenorphine HCl (H-Bupre), or hydromorphone and butorphanol tartrate (H-Butor). Skin temperature and thermal threshold were recorded before (baseline) and for 12 hours after the first injection. Percentage of maximum possible effect (%MPE) and thermal excursion (TE) were compared among treatments and measurement points. Compared with baseline values, skin temperature was higher from 0.75 to 2 hours after the first injection for H-Sal; at 0.5, 1, 3, and 4 hours for H-Bupre; from 0.5 to 3 hours for H-Butor; and from 0.5 to 1 hours for Sal-Sal. Thermal excursion was higher than at baseline from 0.25 to 2 hours for H-Sal and H-Bupre and 0.25 to 0.75 hours for H-Butor; %MPE increased from 0.25 to 2 hours for H-Sal, 0.25 to 3 hours for H-Bupre, and 0.25 to 0.75 hours for H-Butor. Results were similar for comparisons with Sal-Sal, except TE was greater for H-Sal versus Sal-Sal and TE and %MPE were greater for H-Bupre versus Sal-Sal from 0.25 to 1 hours after the first injection. Butorphanol administration decreased the duration of antinociception achieved with hydromorphone administration in cats. This opioid interaction and its impact on pain management require additional investigation.

Analgesic Effect of Tramadol and Buprenorphin in Continuous Propofol Anaesthesia

Abstract The objective of this study was to compare in clinical patients the analgesic effect of the centrally acting analgesics tramadol and buprenorphine in continuous intravenous anaesthesia (TIVA) with propofol. Twenty dogs undergoing prophylactic dental treatment, aged 2−7 years, weighing 6−27 kg, were included in ASA I. and II. groups. Two groups of dogs received intravenous (IV) administration of tramadol hydrochloride (2 mg.kg−1) or buprenorphine hydrochloride (0.2 mg.kg−1) 30 minutes prior to sedation, provided by midazolam hydrochloride (0.3 mg.kg−1) and xylazine hydrochloride (0.5 mg.kg-1) IV. General anaesthesia was induced by propofol (2 mg.kg−1) and maintained by a 120 minutes propofol infusion (0.2 mg.kg−1min−1). Oscilometric arterial blood pressure (ABP) measured in mm Hg, heart rate (HR), respiratory rate (RR), SAT, body temperature (BT) and pain reaction elicited by haemostat forceps pressure at the digit were recorded in ten minute intervals. The tramadol group of dogs showed significantly better parameters of blood pressure (P < 0.001), lower tendency to bradycardia (P < 0.05), and better respiratory rate (P < 0.001) without negative influence to oxygen saturation. Statistically better analgesia was achieved in the tramadol group (P < 0.001). Tramadol, in comparison with buprenorphine provided significantly better results with respect to the degree of analgesia, as well as the tendency of complications arising during anaesthesia.

Factors associated with non-adherence to Buprenorphine-naloxone among opioid dependent African-Americans: A retrospective chart review.

Opioid use disorders are common, chronic relapsing disorders. Buprenorphine (BUP) is an FDA approved medication in the treatment of opioid use disorders, but patient adherence to this medication remains a challenge. To identify risk factors for non-adherence, this chart review study examined the association between DSM-IV Axis I psychiatric disorders, substance use, demographics, and adherence to BUP-naloxone in African-American patients. Charts were selected of patients who had ≥5 visits and completed psychometric screens (Patient Health Questionnaire, Mood Disorder Questionnaire, and a posttraumatic stress disorder questionnaire) at the time of the initial visit (N = 50). Urine drug screens (UDS) were also obtained. Treatment adherence was defined as BUP presence in UDS for ≥80% of the visits. A total of 48% of patients were adherent to treatment. Non-adherent patients had higher rates of use for not only opioids, but also cocaine, and alcohol. Cocaine use was associated with BUP-naloxone non-adherence even after controlling for opioid use. Attendance in cognitive behavioral group therapy sessions (CBT) was significantly associated with adherence. Patients endorsing PTSD symptoms showed higher adherence to treatment compared to those who did not endorse these symptoms. Our results indicate that alcohol and illicit substance use is associated with non-adherence to BUP-naloxone treatment, and suggests that CBT and efforts to promote abstinence from non-opioid substance use may improve adherence among African-Americans. These findings contribute to growing literature on understanding adherence to BUP-naloxone, which is critical to reduce morbidity and mortality.

Clinical Use of Buprenorphine for Anesthesia and Pain Management in Japan

Buprenorphine (BUP) is a classic analgesic drug, and recent studies have reported a new, unique pharmacological profile of it. BUP can be used in patients with renal dysfunction and failure, and these patients can receive the same dose of BUP administered to those with normal renal function. BUP may have a local anestheticlike effect to blockade voltage gated Na+ channels; it can be used as a local anesthetic peripheral nerve block adjuvant to prolong analgesia. BUP is useful for postoperative pain relief in patients with severe liver dysfunction in Japan. However, the prolonged metabolism of BUP and occurrence of delayed emergence from anesthesia may occur in these patients. Moreover, in Japan, the transdermal buprenorphine patch (TBP) is used for the reducing intractable chronic non-cancer pain such as low back pain or pain caused by osteoarthritis not opioid addiction.

A comparative study on post-operative pain relief by intrathecal buprenorphine hydrocholoride with control group

Background: Surgical trauma is a real and severe tissue damage resulting in surgical pain which is a universal phenomenon. Post-surgical pain experienced by patient is often significantly greater than anticipated by the patient. Recognition that inadequate analgesics adversely affect the patient’s cardiovascular, pulmonary and emotional status has spurred development of new and highly effective methods of controlling pain. The benefits of postoperative analgesia are speedy recovery, reduction in physical and mental stress, improvement in pulmonary function (by allowing the patient to cough, breath and move more easily), less stress on cardiac function, decreased incidence of thromboembolic complications. Buprenorphine is a highly lipid soluble narcotic of antagonist agonist type which is 40-50 times more potent than morphine. As per available previous researches, low dose of intrathecal buprenorphine produces prolonged postoperative analgesia with lesser side effects.Methods: The present study was carried out in the department of anaesthesiology, CCM medical college, Durg, Chhattisgarh, India during study period August 2015 to July 2016. The study comprised of 80 patients undergoing surgery of lower abdomen below umbilicus (T10) and lower limbs. Patients of age Group between 20-60 years of age of either sex of ASA group I and II were included in the study. Pre-anesthetic evaluation was done prior to surgery. The patients were randomly divided into 2 groups [group-I (control), group II (Buprenorphine hydrochloride 0.06 mg intrathecally)] of 40 patients each. All the patients were informed about visual analogue scale preoperatively. After the surgical process, observations were recorded. The assessment of results of both groups were done. The results were analysed by unpaired’ test and p value.Results: Mean age in both the groups were comparable and statistically insignificant (p>0.05). Mean age in group I was 39.3±1.5 years and group II was 38.5±12.2. In group II, there was male predominance i.e. M: F was 3: 2, whereas in group I sex ratio was equal (M: F was1:1). Mean weight in both groups were comparable and statistically insignificant (p>0.05). In group I mean weight was 49.5±2.5 kg and 45% pts. Were between 40-50 kg weights. In Group II mean weight was 50.9±8.2 kg and 40% patients were between 40-50 kg weights. Patients receiving study drug has significantly rapid onset of sensory block as compared to control Group (p<0.05). Patients of group II had significantly rapid onset of motor block (p<0.05). The mean duration of surgery in group I was 90.8±44.0, and group II 115.0±40.0 min. The mean duration of motor block in Group I was 190.5±57.2 min and group II was 186.5±30.1 min (3.12+ 0.52 hours). Duration of absolute and effective analgesia is significantly higher in Group II. VAS score is significantly lower in group II patients. There was no statistically significant change in systolic blood pressure, diastolic blood pressure and pulse rate attributable to intrathecal buprenorphine.Conclusions: On the basis of observation and results of our study we conclude that buprenorphine has been found to be superior for postoperative analgesia as compared to control group.

A Study of Method Development, Validation and Forced Degradation for Quantification of Buprenorphine Hydrochloride in a Microemulsion Formulation

Isolation and Identification of Potential Antineoplastic Bioactive Phenolic Compounds in Malaysian HoneysNorjihada Izzah Ismail, Mohammed Rafiq Abdul Kadir, Razauden Mohamed Zulkifli

Differentiating the Effect of an Opioid Agonist on Cardiac Repolarization From µ-Receptor–mediated, Indirect Effects on the QT Interval: A Randomized, 3-way Crossover Study in Healthy Subjects

PurposeA thorough QT study was conducted in healthy subjects to evaluate the effect of buprenorphine hydrochloride administered through a buccal soluble film under coverage of naltrexone to block confounding, secondary QT effects. MethodsHealthy subjects were enrolled in a randomized, partially blinded, 4-way crossover designed study. Subjects received buprenorphine 3 mg with naltrexone, naltrexone alone (with placebo films), placebo (placebo films and placebo naltrexone), and open-label moxifloxacin 400 mg with placebo naltrexone in separate in-house treatment periods. Naltrexone treatment (50 mg) was initiated 12 hours before buprenorphine and was given every 12 hours for a total of 4 doses. ECG data were extracted from a continuous recording predose and serially after dosing on the treatment day. ECG intervals were measured at a central ECG laboratory by using the high-precision QT technique. The QT interval was corrected for heart rate with Fridericia’s formula (QTcF), and change-from-predose baseline QTcF (∆QTcF) was analyzed by using a mixed effect model. FindingsFifty-eight subjects (35 males) with a mean age of 32 were enrolled into the study. Treatment with buprenorphine 3 mg resulted in a small QT effect with the largest mean naltrexone-corrected ∆QTcF reaching 5.8 msec at 8 hours’ postdosing (upper bound of the 90% CI below 10 msec). Exposure response analysis with a linear model demonstrated a significant linear relationship between plasma levels and naltrexone-corrected ∆QTcF, with an estimated mean slope of 0.65 msec per nanogram/milliliter (90% CI, 0.22 to 1.08). Using the exposure response model, an effect on ∆QTcF of 4.5 msec (2.80 to 6.12) can be predicted at the observed geometric peak plasma level after administration of the 3-mg buprenorphine dose in this study (3.6 ng/mL [3.33 to 3.98]). Naltrexone alone did not have a relevant effect on the QTcF interval. ImplicationsThe present study showed that buprenorphine plasma levels up to 5 ng/mL had no effect on the QTc above the level of clinical concern.

Bringing attention to a need for a standardized treatment and weaning protocol for neonatal abstinence syndrome.

Neonatal abstinence syndrome (NAS) due to in-utero opioid exposure has increased 5-fold in the U.S. since 2000, with an incidence of 5.8 per 1,000 live births. NAS now accounts for 3% of all admissions to neonatal intensive care units (NICUs), with associated NICU hospitalization costs of approximately $53,000 per infant. Fifty percent to 80% of opioid-exposed infants require extensive pharmacologic treatment for withdrawal symptoms with an average length of hospitalization of three weeks, with a large range from one week to over a month. This variability is due to a variety of maternal-infant factors such as methadone versus buprenorphine exposure, infant feeding method, ability to room-in with the infant, genetic factors, and co-exposures to nicotine, illicit drugs, and psychiatric medications.

Psychiatric symptoms and treatment outcomes in cocaine-dependent adults treated with buprenorphine and long-acting naltrexone

s / Drug and Alcohol Dependence 156 (2015) e102–e182 e157 Symmetrical discounting of the future and the past in heavy smokers and alcohol drinkers Lara Moody2,1, Warren K. Bickel2 1 Virginia Tech, Roanoke, VA, United States 2 Addiction Recovery and Research Center, Virginia Tech Carilion Research Institute, Roanoke, VA, United

Effect of prewarming on the body temperature of small dogs undergoing inhalation anesthesia.

To investigate whether prewarming affects body temperature of small dogs (weighing < 10 kg [22 lb]) undergoing inhalation anesthesia. Prospective, randomized, blinded clinical trial. Animals: 20 dogs weighing < 10 kg with American Society of Anesthesiologists physical status I or II. Baseline rectal temperature was recorded. Before IM administration of buprenorphine hydrochloride and acepromazine maleate, dogs were randomly assigned to be placed in a pediatric incubator at 33°C (91.4°F) for approximately 30 to 60 minutes (prewarming group) or to receive no prewarming (control group); subsequently, dogs underwent inhalation anesthesia with isoflurane in oxygen. Rectal, esophageal, and ambient temperatures were measured every 5 minutes from induction of anesthesia (IOA) for > 1 hour by an observer who was unaware of treatment. If a dog became hypothermic (esophageal temperature < 36°C [96.8°F]), it was withdrawn from the study. Variables of interest relating to dogs, anesthesia, temperatures, hypothermia, and study withdrawal were compared between groups. 1 dog was excluded from the prewarming group after becoming excessively excited in the incubator. Between groups, age, weight, body condition score, degree of preanesthesia sedation, interval from sedation to IOA, duration of anesthesia, baseline rectal temperature, rectal temperatures immediately prior to IOA, esophageal temperature following IOA, ambient temperature during the first 70 minutes of anesthesia, esophageal or rectal temperature during the first 90 minutes of anesthesia, and incidence of hypothermia and study withdrawal (5 dogs/group) did not differ significantly. Prewarming in an incubator prior to IOA failed to improve or maintain body temperature of dogs weighing < 10 kg during inhalation anesthesia.

AATOD and ASAM on revising buprenorphine regulations

AATOD and ASAM on revising buprenorphine regulations

Effects of premedication with sustained-release buprenorphine hydrochloride and anesthetic induction with ketamine hydrochloride or propofol in combination with diazepam on intraocular pressure in healthy sheep.

To determine the effects of diazepam combined with ketamine hydrochloride or propofol for induction of anesthesia (IOA) following premedication with sustained-release buprenorphine hydrochloride (SRB) on intraocular pressure (IOP) in sheep. 20 healthy adult sheep. Diazepam with ketamine or propofol was given IV to each of 10 sheep after premedication with SRB (0.01 mg/kg, SC); after > 4 weeks, each sheep received the other induction combination with no premedication. For both eyes, IOPs were measured before premedication (if given), 10 minutes prior to (baseline) and immediately following administration of ketamine or propofol (time of IOA), after endotracheal intubation, and 5 minutes after IOA. Peak end-tidal P(CO2), globe position, and pupillary diameter were also analyzed. Data were not available for all sheep for all anesthetic episodes. Propofol-diazepam administration alone had no significant effect on IOP, whereas there was a significant decrease in IOP immediately following ketamine-diazepam administration alone. At 5 minutes after ketamine-diazepam administration, SRB-premedicated sheep had significantly higher IOP than unpremedicated sheep. Intraocular pressure was significantly higher at baseline, at intubation, and 5 minutes after IOA in SRB-premedicated sheep receiving propofol-diazepam, compared with unpremedicated sheep. Peak end-tidal P(CO2) at intubation was significantly higher in SRB-premedicated sheep. For sheep receiving either anesthetic treatment, IOPs did not differ significantly with or without SRB premedication. Globe position or pupillary diameter and IOP were not significantly related at any time point. Results suggested that both ketamine-diazepam and propofol-diazepam combinations were suitable for IOA without increasing IOP in sheep. The use of SRB should be avoided in sheep when increases in IOP are undesirable.

Urine analysis of buprenorphine/norbuprenorphine/ naloxone in drugs and driving cases

It was Robinson who elucidated the active structure of morphine in 1925. Buprenorphine (2S)-2-[(5R,6R,7R,14S)-9αCyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6methoxymorphinan-7-yl]-3,3-dimethylbutan-2-ol) which is a semi-synthetic opioid. It possesses partial agonist properties acting at μ-opioid receptor site, it also possesses antagonist characteristics acting mainly on the κ-opioid receptor site [1]. Its structure is derived from thebaine, and it has a structural similarity with morphine ((5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol), but has been reported to be up to 50 times more potent, with a higher affinity for μ-opioid receptors compared with other opioids, including heroin (diacetyl morphine)[2]. Historically, buprenorphine was first synthesized 1966 by John Lewis working at Reckitt and Colman (later Reckitts). Lewis had previously been a doctoral student of Sir Robert Robinson, who had elucidated the active structure of morphine in 1925 [3]. Buprenorphine (BUP) is metabolized in human beings through to the active metabolite norbuprenorphine (NBUP) via the process of N-dealkylation, performed primarily by cytochrome P450 (CYP 450) 3A4 and CYP 2D6 groups of enzymes [4]. Minor metabolites of BUP and NBUP i.e hydroxybuprenorphine and hydroxynorbuprenorphine have also been reported [5], these are believed to occur after oxidation of the tertiary butyl group on both BUP and NBUP but do not make a significant contribution to the urinary profile. Peak plasma concentration times of BUP have reported to range from 0.66 hours to 3.5 hours, its halflife (t1/2) has been reported to be as long as 44 hours [6]. NBUP the primary metabolite of buprenorphine is by nature is a weak opiate agonist and has been reported as having a potency of one quarter of buprenorphine. It has also been reported that it possesses greater respiratory depressant effects than the parent and this phenomenon may controlled not by brain based opioid receptors but those located in the lung [7]. The half-life for NBUP JOURNAL OF APPLIED BIOANALYSIS, July 2015, p. 80-88. http://dx.doi.org/10.17145/jab.15.014 (ISSN 2405-710X) Vol. 1, No. 3

The introduction of buprenorphine-naloxone film in opioid substitution therapy in Australia: Uptake and issues arising from changing buprenorphine formulations.

Buprenorphine-naloxone (BNX) film for opioid dependence treatment was introduced in Australia in 2011. A key difference in State policy approaches saw transfer from BNX tablets to BNX film mandated in South Australia (SA) with New South Wales (NSW) and Victoria (VIC) having less stringent policies. This study examined (i) how initiations and transfers were implemented, (ii) the profile and predictors of adverse effects as self-reported by BNX film clients, and (iii) dosing issues. Survey of 334 buprenorphine (BPN), BNX tablet and BNX film clients and semi-structured interviews with 39 key experts (KEs) in 2012. Comparisons are made between clients interviewed in SA versus NSW and VIC combined. Among the 180 current BNX film clients, 23% started treatment on BNX film, 18% requested a transfer to BNX film and 59% (n = 106) reported their clinic/prescriber recommended transfer to BNX film. Among clients who were offered but refused a transfer to BNX film (n = 66), the most common reason was 'I am happy with my current treatment and do not see a reason to change' (53%). Some opioid substitution therapy clients and KE viewed transfers as 'forced' (i.e. no choice of buprenorphine formulation). Multivariable regression showed residing in SA (vs. NSW/VIC) and a shorter length of current treatment episode were associated with more BNX film-attributed adverse effects but clinic/prescriber-recommended transfer was not. The introduction of BNX film in Australia varied across States. A perception of restricted choice in medication may have undermined initial acceptance in SA.

Pharmacokinetic and pharmacodynamic evaluation of high doses of buprenorphine delivered via high-concentration formulations in cats.

To evaluate the potential benefits of high-dose buprenorphine formulations for analgesia in cats, serial and crossover studies were undertaken to investigate their pharmacokinetics and thermal antinociceptive effects. Twelve healthy adult domestic shorthair cats (6.0 ± 1.1 kg body weight) were studied. Aqueous solutions of buprenorphine hydrochloride at 0, 0.02, 0.06, 0.12 and 0.24 mg/kg body weight and formulations containing 0, 0.3, 0.6 and 1.2 mg/ml with and without preservatives were given subcutaneously. Blood samples were taken and thermal threshold (TT) measured prior to and at regular time points up to 72 h after dosing. Descriptive statistics and analyses of variance were applied as appropriate. Baseline TT was 47.6 ± 4.1°C, which increased in all groups treated with all buprenorphine dosages and formulations. After doses of 0.12 mg/kg and above, TT was significantly higher than baseline at most time points from 1-30 h post-treatment. The time to maximum effect (Tmax) ranged between 0.25 and 2.00 h; and plasma concentrations associated with maximum antinociceptive effect (Cmax) were 1.01-1.72 ng/ml after the 0.02 mg/kg dose, 1.4-4.9 ng/ml after the 0.06 mg/kg dose, 4.6-51.4 ng/ml after the 0.12 mg/kg dose and 5.3-22.3 ng/ml after the 0.24 mg/kg dose. The range of estimates for the buprenorphine elimination half-life were as follows: 0.02 mg/kg = 1.35-5.33 h; 0.06 mg/kg = 16.1-31.2 h; 0.12 mg/kg = 10.1-34.0 h; and 0.24 = mg/kg 16.1-31.6 h. The mean 'plasma concentration for the offset of analgesia' was 2.3 ± 2.0 ng/ml. No adverse effects were seen. The addition of preservatives to a high-concentration buprenorphine formulation had no impact on antinociception nor any side effects. Aqueous high-concentration buprenorphine formulations administered at 0.12 or 0.24 mg/kg have potential for clinical use in cats, providing prolonged antinociception in a single subcutaneous injection of minimal dose volume.

To Be Free and Normal: Addiction, Governance, and the Therapeutics of Buprenorphine

To Be Free and Normal: Addiction, Governance, and the Therapeutics of Buprenorphine

Comparison of Opioid Antagonist Modulation of Buprenorphine‐Induced Neurochemical Changes

ObjectiveEvaluate differences in onset and duration of action of µ‐opioid antagonists on buprenorphine (BUP)‐induced elevations of nucleus accumbens shell (NAc‐sh) neurotransmitters.Methods: Studies utilized male Wistar rats (275 ‐ 375g) with microdialysis probes inserted into the NAc‐sh (A/P +1.70; M/L ±0.8; D/V ‐7.8 from bregma). Bioanalytical analyses of dopamine (DA) and its metabolites 3,4‐dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were performed using HPLC‐EC. Data were converted to percent change from baseline and analyzed using a repeated measures two‐way ANOVA and mechanistic pharmacodynamic modeling.Results: BUP (0.1 mg/kg) elevated extracellular concentrations of DA, DOPAC and HVA in the NAc‐sh for approximately 20 hours after subcutaneous administration. Co‐administration of either samidorphan (SAM) or naltrexone (NTX) (0.3 ‐ 3.0 mg/kg) dose dependently attenuated BUP‐induced dopaminergic activity. However, the temporal pattern of this attenuation was different for NTX and SAM. NTX displayed a rapid Kon and Koff resulting in an immediate but short‐lived (~4 hours) attenuation of BUP's effects. SAM displayed a longer Kon and Koff resulting in a protracted but longer‐lasting (~8‐10 hours) attenuation of BUP's effects.ConclusionsDifferences observed between SAM and NTX in onset and duration of action were not predicted by in‐vitro pharmacology or pharmacokinetic profiles. Importantly, the duration of action reported previously in humans for both antagonists is much longer than in rats. These data illustrate the importance of understanding the duration of action when assessing the activity of different opioid antagonists in nonclinical models.

Congressman Murphy blasts methadone and buprenorphine

Congressman Murphy blasts methadone and buprenorphine

Clonidine Helps to Maintain Opioid Abstinence

Despite buprenorphine treatment, opiate-dependent individuals are at risk for relapse, particularly during stressful periods. In a study based on

Determination of buprenorphine, norbuprenorphine and naloxone in fingernail clippings and urine of patients under opioid substitution therapy.

The aim of this study was to develop and validate a method for the determination of buprenorphine (BUP), norbuprenorphine (NBUP) and naloxone (NAL) in fingernails and urine samples collected from former heroin users under suboxone substitution therapy. The analytes were extracted by solid-liquid or solid-phase extraction and were analyzed by liquid chromatography-mass spectrometry. The validation of the analytical methods developed included linearity, recovery, accuracy, precision, ion suppression, sensitivity of interfaces and limits of determination and quantification. The validated methods were applied to samples from 46 individuals. The majority of the urine samples were positive for all analytes (93.5% for BUP, 95.7% for NBUP and 84.8% for NAL). In nails, a higher detection rate was observed for NBUP and BUP (89.1%), compared with NAL (10.9%). The median values of the NBUP/BUP and the NAL/BUP ratio were 2.5 and 0.3 in urine and 0.8 and 0.3 in nails, respectively. A statistically significant correlation was found between the BUP, NBUP and total BUP (BUP and NBUP) concentrations in urine and those in nails. A weak correlation was observed between the daily dose (mg/day) and total BUP (P = 0.069), or NBUP (P = 0.072) concentrations in urine. In contrast, a strong correlation was found between the total amount of BUP administered during the last 12 months and total BUP (P = 0.038), or NBUP (P = 0.023) concentrations in urine. Moreover urine BUP, NBUP and total BUP concentrations correlated significantly. Our study demonstrated successfully the application of the developed method for the determination of the three analytes in urine and nails.