Concentrations Of Pentazocine Research Articles

SIMULTANEOUS QUANTIFICATION OF PENTAZOCINE AND NALOXONE BY STABILITY INDICATING REVERSE-PHASE-HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC METHOD

Objective: The objective of the study was to develope a stability indicating high-performance liquid chromatographic (HPLC) method for simultaneous assay of pentazocine and naloxone in bulk and tablets.
 Methods: Pentazocine and naloxone were analyzed on Dionex C18 column using 0.1M K2HPO4 buffer (pH 4.0) and methanol (60:40, v/v) as the mobile phase. The concentration of pentazocine and naloxone was quantified by photodiode array detector set at 248 nm. The method was validated in compliance with ICH rules. Pentazocine and naloxone tablet formulation was subjected to forced degradation such as acid, neutral and alkali hydrolysis, oxidation, photo, and thermal degradation.
 Results: The method was linear, with R2=0.9999 in the concentration range 100–300 μg/ml for pentazocine and R2=0.9995 in the concentration range 1–3 μg/ml for naloxone. The level of detection and quantification was 0.097 μg/ml and 0.322 μg/ml for pentazocine and 0.0073 μg/ml and 0.0243 μg/ml for naloxone, respectively. The degraded products are resolved well from pentazocine and naloxone with significantly different retention time values. From validation results, it was proved that the method is selective, precise, robust, and accurate for the estimation of pentazocine and naloxone simultaneously.
 Conclusion: The developed stability-indicating HPLC method can be applied for quantitative determination of pentazocine and naloxone in tablets.

Sensitive determination of pentazocine in human tissues by high-performance liquid chromatography

The authors developed a simple, reliable and sensitive method for the determination of pentazocine in human solid tissues using high-performance liquid chromatography, combined with a three-step liquid-liquid extraction procedure. Levallorphan tartrate served as the internal standard. The extract was evaporated to dryness and dissolved in the mobile phase of acetonitrile/10 mM phosphate buffer (pH 4.0). The eluent was pumped at a flow rate of 0.4 ml/min through a Spherisorb R Ph (2.1 mm I.D. × 150 mm) column. A fluorescence detector with excitation at 247 nm and emission at 320 nm was used. The lower limit of detection was about 0.5 ng/g. The calibration curve was linear over the concentration ranges from 1 to 500 ng/g in each tissue examined and could be determined up to at least 10.0 μg/g by means of reduction of injected volumes. Using this method, the concentrations of pentazocine could be determined in the tissues of an autopsied individual for toxicological evaluation.

Liquid chromatography–fast atom bombardment mass spectrometry for detection and determination of pentazocine in human tissues

A reliable and sensitive method was developed for the detection and determination of pentazocine in human solid tissues using liquid chromatography–dynamic fast atom bombardment (FAB) mass spectrometry, combined with a three-step liquid–liquid extraction procedure. Levallorphan tartrate served as an internal standard. The extract was evaporated to dryness and dissolved in the mobile phase, acetonitrile–10 mM ammonium acetate solution (20:80, pH 4.0) containing 0.5% glycerol as FAB matrix. The eluent was pumped at a flow rate of 25 μl/min and split before introduction to FAB mass spectrometer. Quantitative analysis was carried out by means of monitoring quasi-molecular ions with m/z 286 for pentazocine and m/z 284 for levallorphan. The lower limit of detection of pentazocine in each tissue tested was 1 ng/g with scan mode and 0.1 ng/g with SIM mode. Using this method, the concentrations of pentazocine were determined in the tissues of an autopsied individual to perform toxicological evaluation.

Pharmacokinetics of pentazocine and its occupancy of opioid receptors in rat brain.

In order to assess quantitatively the pharmacodynamic process of pentazocine (PTZ), time courses of its plasma concentration and of the occupation of specific opioid receptors in the brain were investigated after intravenous (i.v.) administration of PTZ to rats. The plasma concentration of PTZ was determined by HPLC and the pharmacokinetic parameters were analyzed using nonlinear least-squares analysis. Measurement of ex vivo receptor occupation was made by comparing the specific [3H]naloxone (opioid receptor antagonist) binding in vitro to the crude P2-synaptosomal fractions between vehicle-treated rats (control) and PTZ-treated rats. Following the i.v. administration of PTZ, the occupancy of specific opioid receptors decreased rapidly until 10 min, depending on the two pharmacological doses (2.5 and 10 mg/kg). The results strongly suggest the fast binding kinetics of PTZ in terms of its association with and dissociation from specific opioid receptor sites in the brain in addition to its fast rate of disappearance from the brain compartment. Furthermore, we demonstrated that the time profile of receptor occupancy correlated well (r = 0.8650) with that of the unbound concentration in plasma until 120 min after the i.v. administration of PTZ to rats.

Application of high-performance liquid chromatography with electrochemical detection for monitoring the concentration of pentazocine in human blood

Application of high-performance liquid chromatography with electrochemical detection for monitoring the concentration of pentazocine in human blood

Pharmacokinetic studies of the inhibition of glucuronization of pentazocine by salicylamide.

The serum concentrations of unchanged and glucuronized drug were determined after intravenous injection of pentazocine (PA) in rabbits. A compartment model isolating the liver from the central compartment was proposed to explain the observed time courses of the concentration, and the resulting convolution equation was M (t)=∫10D (t-θ) G (θ) dθ, where M (t) and D (t) are the serum concentrations of glucuronized PA and unchanged PA after intravenous injection, respectively. The weight function, G (t), which represents the response for a pulse input of glucuronized PA was estimated to be G (t)=0.00933 (e-0.00818t-e-0.223t) (min-1). The simultaneous intravenous administration of salicylamide (SAM) had no effect on the glucuronization of PA in serum. The serum concentration of glucuronized PA calculated by numerical convolution of G (t) and the published serum concentration of unchanged PA after oral administration represents that of glucuronide produced from the unchanged PA which escaped the first-pass effect. This calculated value was far below the published serum concentration of glucuronized PA after oral administration, and the difference represents the glucuronized PA produced by the first-pass effect. The area under the concentration-versus-time curve of glucuronized PA produced by the first-pass effect was 274 times larger than that of glucuronized PA produced from unchanged PA in the serum. Simultaneous oral administration of SAM only inhibits the first-pass effect.

Physiological pharmacokinetic model for distribution and elimination of pentazocine. II. Study in rabbits and scale-up to man

A physiologically based pharmacokinetic model was applied to describe the distribution and elimination of pentazocine in rabbits. For the elimination of pentazocine, the model consisted of renal, hepatic (metabolic and biliary), and GI secretion and Gl re-absorption. The tissue-to-blood partition coefficients of pentazocine in the rabbit were almost the same with those in the rat. No significant variation in hepatic blood flow rate dependent on the arterial blood concentration of pentazocine was observed in the rabbit, the results being very different from those in the rat. The time course of blood concentration after intravenous injection was proportional to dose in the range of 0.5–10 mg/kg. Excellent agreements were obtained between the predicted and observed concentrations of pentazocine after intravenous administration in the rabbit. Application of the rabbit model to prediction in man by considering the differences in organ volume, organ blood flow and renal pentazocine clearance was successful, and the model was adopted to decide the therapeutic dose of pentazocine during surgery of patients.

Relative Bioavailability and Pharmacokinetics: A Combination of Pentazocine and Acetaminophen

The relative bioavailability and pharmacokinetics of a combination product containing pentazocine and acetaminophen were studied in 20 healthy human males. Each subject, in a single-dose three-way crossover design, received two different preparations containing 50mg of pentazocine (as base) and 1300mg of acetaminophen either as capsule-shaped tablets or as a solution. Plasma concentrations of pentazocine and acetaminophen were determined from 0.25 to 12h following oral administration. The plasma data for both compounds in the tablet formulation were described by an open one-compartment body model with first-order absorption. The average (±SD) bioavailability of the tablet relative to that of the solution was 85.0 ± 31.1 and 88.6 ± 13.1% for pentazocine and acetaminophen, respectively. The apparent first-order regression-dependent elimination rate constants for pentazocine from the tablet and solution preparations were 0.19 ± 0.08 and 0.20 ± 0.06h−1, respectively, while the rate constants for acetaminophen were 0.26 ± 0.03 and 0.25 ± 0.03h−1 for the tablet and solution preparations, respectively. These rate constants correspond to terminal elimination half-lives of ~3.6h for pentazocine and ~2.7h for acetaminophen.

Two-phase derivatization of pentazocine with chloroformate esters and determination by gas chromatography

Two-phase derivatization with chloroformate esters of tertiary amines that contain a phenol group has been studied. The derivatives were analysed by gas chromatography with sensitive and selective detectors. The N,O-bis derivative of pentazocine was formed using an aqueous phase at pH 9.8, with tetrabutylammonium ion for extraction of the phenolate ion as an ion-pair. The organic phase comprised methylene chloride with trichloroethyl chloroformate or ethyl chloroformate. At pH 10.7 the derivative was hydrolysed by hydroxide ions extracted into the organic phase. Hydrolysis also occurred when more lipophilic counter-ions such as tetrapentyl-ammonium ions were used. Two-phase derivatization could also be achieved with toluene or ethyl acetate as the organic phase, although the reaction rate was considerably slower. The method was also applied to the assay of pentazocine in plasma. The best results were achieved after selective extraction of pentazocine from plasma, two-phase derivatization with ethyl chloroformate and determination by mass spectrometry or thermionic detection. The minimum detectable concentration of pentazocine was 10 ng/ml in a 1-ml plasma sample.

Physiological pharmacokinetic model for pentazocine. I. Tissue distribution and elimination in the rat

A physiologically based pharmacokinetic model was developed to describe the tissue distribution and elimination of pentazocine in the anesthetized rat. The model incorporates renal and hepatic (metabolic and biliary) elimination, GI secretion, GI reabsorption and tissue-to-blood partition coefficients. The dependency of hepatic blood flow rate on the arterial blood concentration of pentazocine is also included in the model. Excellent agreement was obtained between the predicted and observed concentrations of pentazocine in tissues and in arterial blood after a 2 mg/kg intravenous dose. Non-linear dose-dependent blood concentration-time profiles after intravenous injection of 0.5–10.0 mg/kg were successfully interpreted with the present model.

Spontaneous Live Birth with a Maternal History of Intravenous Use of Pentazocine and Tripelennamine (T's and Blues)

A 24-year-old black female presented a live birth of six-months gestation. The 700-g neonate survived for 11 h. After toxicology revealed the presence of pentazocine and tripelennamine (T's and Blues), the mother admitted to using this combination intravenously 9 h previous to admission. Concentrations of pentazocine and tripelennamine were simultaneously determined by gas-liquid chromatography (GLC) combined with nitrogen selective detection. Analyses were performed on a 3% OV-101 column, with the added internal standard, dexbrompheniramine. Both pentazocine and tripelennamine were qualitatively confirmed by their electron impact mass spectra. Concentrations of pentazocine and tripelennamine in various fluids and tissues were determined.

医薬品の生物薬剤学的研究(第1報)経口投与時におけるPentazocineの血清中濃度におよぼすSalicylamideの併用効果

The serum concentration of unchanged pentazocine (PA) was investigated in rabbits when PA was administered concurrently with acetaminophen, salicylamide (SAM), salicylic acid, acetylsalicylic acid, or p-aminosalicylic acid. The serum concentration of unchanged PA increased when 20 mg/kg PA was administered concurrently with 80 mg/kg SAM as compared with the administration of 20 mg/kg PA alone, but no similar results were obtained with the other drugs. The co-administration of PA and SAM also decreased serum and urinary PA glucuronide. On the other hand, when 80 mg/kg SAM and 375.6 mg/kg PA were administered together, the serum and urinary concentration of unchanged SAM was increased, while SAM glucuronide was decreased. We posit that the effect noted in the simultaneous 20 mg/kg PA and 80 mg/kg SAM administration experiments is due to competitive inhibition of glucuronidation.

The relation between pain and personality in patients receiving pentazocine (fortral) after surgery

This paper reports the relationship between post-operative pain and personality in patients receiving pentazocine (Fortral) for pain relief. The drug was given to 26 men with lumbar disc disease who were otherwise healthy. Peak concentrations of pentazocine in the blood occured within approximately an hour of intramuscular injection and this coincide with the time of greatest pain relief. At this point also variations in pain, if related to the Neuroticism and Extraversion dimensions of personality, were insignificant. However, as the concentration of pentazocine fell the influence of personality became obvious. Patients with either high levels of neuroticism or extraversion had more pain than their fellows and the greatest differences in pain scores occured if those with both high levels of neuroticism and extraversion were compared with the remainder. It is concluded that regular prescription of analgesic drugs of adequate potency is preferable to an “on demand” schedule and that the beneficial effects of the former in reducing patients' anxiety about relief of pain colud be enhanced by other means.

Pentazocine binding to blood cells and plasma proteins.

The binding of pentazocine to human whole blood, plasma, and blood cells was investigated in 20 normal subjects and 22 patients by means of equilibrium dialysis. Plasma protein binding was 56% to 66% in the control sub;ects and 48% to 75% in the patients. In control sub;ects, 48% of the total amount of pentazocine in whole blood is present in blood cells and 33% is bound to plasma proteins. The remaining 19% is in the plasma water. Whole blood concentrations of pentazocine may be expected to be about the same as the plasma concentrations in sub;ects with normal hematocrit.

Distribution of pentazocine in blood and brain of the baboon following intravenous injection.

1 In the baboon the blood levels of pentazocine between 1 and 60 min after intravenous injection of 0.5 mg/kg were measured by a gas chromatographic technique. From cerebral arteriovenous differences it was shown that the peak of the brain concentration occurred within 15 min and probably within 10 min of intravenous injection. At the time of peak concentration about 10% of the injected dose was in the brain, while the corresponding value at 60 min was 2%.2 The concentration of pentazocine in the brain was an order of magnitude greater than the concentration in cerebral venous blood both at 5 min and 60 min after injection. No major brain interregional differences were demonstrated. Cerebrospinal fluid from the cisterna magna did not yield values from which the cerebral concentration of pentazocine could be predicted.

Plasma and cerebrospinal fluid concentrations of pentazocine in patients: assay by mass fragmentography.

Abstract Mass fragmentography has been used for the determination of low concentrations of pentazocine in blood plasma and cerebrospinal fluid (csf) after intravenous administration of a 30 mg dose to eight patients undergoing neurosurgery under general anaesthesia. A pharmacokinetic analysis based upon mean plasma levels indicated a half-life of 134 min. Lumbar csf levels of pentazocine increased rapidly with mean values from about 3 ng ml−1 at 5 min to 10 ng ml−1 at 30 min and to about 15 ng ml−1 at 90–120 min. The possibility of repeated analyses of drug concentrations in the csf represents an important step towards the correlation of chemical data with clinical effects for centrally acting drugs.

Pharmacokinetics of pentazocine in the rhesus monkey

The time course of pentazocine concentration was followed in the plasma and cerebrums of individual monkeys by obtaining serial samples of both tissues after intravenous administration of tritiated drug. Plasma concentrations of pentazocine were also followed in a monkey after portal vein infusion. A three-compartment open-system model adequately fits the observed plasma data. The use of the constants derived from that model to predict the time course of pentazocine concentration in the brain results in a good fit with the observed cerebral concentrations. As expected, portal vein infusion caused a reduction in the area below the plasma concentration-time curves and in the percentage of pentazocine excreted in the urine. The relative proportions of known metabolites and their conjugates in urine were determined.

Serum and brain concentrations of pentazocine in relation to analgesic activity in mice

Abstract Serum and brain concentrations of pentazocine and its metabolite, the trans-alcohol, have been studied in mice and related to analgesic activity. The concentrations were determined fluorometrically after extraction and isolation of the compounds by partition chromatography as ion pairs. The acute intravenous toxicity (LD50) of the drug was also determined. The analgesic activity was found to reside in the unchanged pentazocine since, after the initial distribution phase, the drug elicits a higher degree of analgesia in animals showing higher brain concentrations of pentazocine. Furthermore, animals which did not show an analgesic response had higher serum concentrations of the trans-alcohol in comparison with animals showing analgesic activity, indicating a relation between analgesia and the degree of metabolism. However, the relation between the analgesic response and the brain concentration during the first 20 min after intravenous injection of the drug was poor.

The uptake of pentazocine into brain

A simple procedure for the extraction from tissues and determination by gas chromatography of pentazocine was developed. The mean recovery from brain was 96%. The time- and dose-dependent uptake of pentazocine into the brain was investigated and correlated with the plasma levels of the drug. The results showed a rapid entry of pentazocine into the drug. The results showed a rapid entry of pentazocine into at 2 min and 10 min, respectively, after the i.p. administration. After the injection of a single dose, the ratio, concentration of pentazocine in plasma/concentration of pentazocine in brain was constant from 10–90 min. This ratio remained unchanged over the range of 25–100 mg/kg of administered drug.