• Journal of Pharmaceutical Investigation
• /
• 제9권3호
• /
• pp.9-21
• /
• 1979

This study was undertaken to establish the different pharmaceutical properties between promethazine HCl and promethazine pamoate. First, promethazine pamoate was prepared by using the modified method of Saias. Second, in order to study the different pharmacokinetics between promethazine pamoate and promethazine HCl, absorption rate, plasma concentration, and distribution, as well as urinary excretion of the both compounds were examined in rabbits as an experimental animal: The results were as follows. 1. In the in vitro isolated intestine of rabbit, the rate constant for absorption of promethazine pamoate was $0.347hr^{-1}$ and that of promethazine HCl was $0.532hr^{-1}$. 2. After oral administration of promethazine pamoate, the increase of plasma concentration of promethazine was much slower than that of promethazine HCl. 3. The urinary excretion rate of promethazine pamoate was significantly low in comparison to that of promethazine-HCl; i. e. about 50% of promethazine HCl was excreted within 3 hours, and 5 to 15 hours for that of promethazine pamoate. 4. The tissue concentration of promethazine after oral administration of promethazine pamoate in rabbit was steadily increased for 5 hours. However, promethazine HCl concentration reached to maximum 1 hour after administration, then decreased slowly. 5. A significant amount of promethazine was mainly distributed in spleen, kidney, lung, liver and heart in this order, rather than other organs, such as brain, and muscle. 6. In the toxicity test by using mouse, $LD_{50}$ for promethazine pamoate was 3,250 mg/kg, while $LD_{50}$ for promethazien HCl was 298mg/kg.

• Journal of Pharmaceutical Investigation
• /
• 제36권1호
• /
• pp.23-29
• /
• 2006

A rapid, selective and sensitive reversed-phase HPLC method for the determination of promethazine in human serum was developed, validated, and applied to the pharmacokinetic study of promethazine. Promethazine and internal standard, chlorpromazine, were extracted from human serum by liquid-liquid extraction with n-hexane containing 0.8% isopropanol and analyzed on a Capcell Pak CN column with the mobile phase of acetonitrile-0.2 M potassium dihydrogen phosphate (42:58, v/v, adjusted to pH 6.0 with 1 M NaOH). Detection wavelength of 251 nm and flow rate of 0.9 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^{3}$ factorial design using a fixed promethazine concentration (10 ng/mL) with respect to its peak area and retention time. In addition, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 1-40 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 1 mL of serum was 1 ng/mL, which was sensitive enough for pharmacokinetic studies. The overall accuracy of the quality control samples ranged from 96.15 to 105.40% for promethazine with overall precision (% C.V.) being 6.70-11.22%. The relative mean recovery of promethazine for human serum was 63.54%. Stability (freeze-thaw and short-term) studies showed that promethazine was stable during storage, or during the assay procedure in human serum. However, the storage at $-80^{\circ}C$ for 4 weeks showed that promethazine was not stable. Extracted serum sample and stock solution were not allowed to stand at ambient temperature for 12 hr prior to injection. The peak area and retention time of promethazine were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of promethazine in human serum samples for the pharmacokinetic studies of orally administered Himazin tablet (25 mg as promethazine hydrochloride) at three different laboratories, demonstrating the suitability of the method.

• 약학회지
• /
• 제23권1호
• /
• pp.41-49
• /
• 1979

By intraperitoneal administration of thioacetamide to rats, acute liver injury was produced. In these rats, the level of serum GOT and GPT activities showed a remarkable increase and the principal histopathologic change was centrilobular hepatic necrosis. In this study, combined administration of silymarin with promethazine hydrochloride to the rats with acute liver injury which was produced by thioacetamide inhibited the increase of serum transaminase activities and protected the histopathologic change, showing comparatively more improved results than simple administration of silymarin alone. On the basis of these results, it is suggested that promethazine hydrochloride potentiates the effectiveness of silymarin in acute thioacetamide hepatotoxicity of rats.

• 대한화학회지
• /
• 제58권2호
• /
• pp.227-229
• /
• 2014

• 대한약침학회지
• /
• 제23권1호
• /
• pp.18-24
• /
• 2020

Objectives: Pain is considered as a cause of sickness and the most prevalent symptom which makes people visit a physician. Nowadays, combination therapy is becoming useful to relieve chronic and postsurgical pain. The aim of this study was to study the promethazine (as an antihistamine) interactions with antinociceptive effect of diclofenac (as a non-steroidal anti-inflammatory drugs). Methods: In initial part of the study, we investigate the analgesic effect of diclofenac. Using writhing test, we demonstrate that diclofenac significantly reduces writhe response induced by acetic acid in a dose-dependent manner. In this study, we evaluate the combination effect of promethazine on diclofenac analgesic effect. Results: We observed that diclofenac inhibited pain in the dose dependent manner which means that by increasing dose of diclofenac a significant decrease in pain was observed. This experimental setup allowed calculation of the dose that caused 50% antinociception (ED50) for diclofenac. The ED50 for diclofenac in this study was determined to be 9.1 mg/kg according our previous study. Additionally, promethazine was showed a dose-dependent inhibition of writhes. The combination of different doses of promethazine (2, 4, 6 mg / kg) with diclofenac ED50 (9.1 mg / kg) was injected to mice. Promethazine 4 and 6 mg / kg in combination with diclofenac had significantly led to increase analgesic effect of diclofenac. Conclusion: In conclusion, these results add important information to the existing knowledge on combination of diclofenac and antihistamine in pain therapies to be used in clinical practice and maybe helpful in designing the future guidelines.

• Biomolecules & Therapeutics
• /
• 제13권2호
• /
• pp.118-122
• /
• 2005

The objective of the present investigation was to study pharmacokinetics of promethazine in Korean healthy subjects using a validated HPLC method. The HPLC analysis was performed on a Capcell Pak CN column with a mixture of acetonitrile-0.02M potassium dihydrogen phosphate (42:58, v/v, pH 6.0) and the analyte was quantified with UV detection at 251 nm. The calibration curve of the drug was linear over the range of 1-40ng/mL in human serum and the limit of quantification (LOQ) was 1 ng/mL. This analytical method was validated and shown to be specific, accurate, precise and reproducible. This method was applied to pharmacokinetic study of promethazine in Korean healthy volunteers following an oral administration of two 25 mg Himazin tablets (50 mg promethazine ${\cdot}$HCI) after overnight fasting. Serum samples were collected at given intervals over a 36-hour period (12 points) and pharmacokinetic parameters were determined from serum concentration-time profile using WinNonlin program. The estimated $AUC_{0__\infty}$, $AUC_{0_\infty}$, $C_{max}$, $T_{max}$ and $t_{1/2}$ of promethazine obtained from Korean healthy subjects were 103.84 ${\pm}$84.30 ng${\cdot}$hr/mL, 87.94${\pm}$81.02 ng${\cdot}$hr/mL, 13.43${\pm}$10.92 ng/mL, 2.00${\pm}$1.16 hr and 5.88${\pm}$3.47 hr, respectively.

• 한국식품위생안전성학회지
• /
• 제13권3호
• /
• pp.232-237
• /
• 1998

광독성 및 광알러지를 일으키는 물질인 phenothiazine계 약물중 chlopromazine(CPZ), perphenazine(PPZ), trifluoperazine(TFZ), promethazine(PMZ)을 택하여 적혈구에서의 광용혈현상을 Kahn 등의 방법에 의하여 UVB(UV irradiation RMX-3W, $1.5\;J/\textrm{cm}^2$)을 조사하여 약물 농도별로 측정한 결과 CPZ, PPZ은 UVB 조사에 의해 약물농도에 따라 현저히 적혈구 용혈현상이 증가 되었으며 이는 ascorbic acid에 의해 유의성 있게 감소되었고, 각 약물의 광독성 물질 생성 여부와 이에 의한 용혈독성을 조사해 보니 CPZ, PMZ에서 관찰되었고 ascorbic acid에 의해 그 현상이 감소되었다.

• Toxicological Research
• /
• 제3권2호
• /
• pp.81-88
• /
• 1987

Hepatotoxicity study of the nitrosamine produced by interaction between drugs containing amino groups and soduim nitrite was conducted. In the in vitro study, interaction of 32mM Promethazine HCL or Oxomemazine HCL with 200mM Sodium nitrite produced N-nitroso dimetylamine (NDMA) at 0.4% or 0.03%, respectively. When sodium nitrite was administered with Promethazine HCL or Oxomemazine HCL, trace of NDMA was detected from the gastric contents. After three days of consecutive administration of sodium nitrite with Promethazine HCL or Oxomemazine HCL, the levels of GOT, GPT and SDH in the serum of treated groups were significant higher than that of control group.

• 한국식품영양과학회지
• /
• 제5권1호
• /
• pp.65-68
• /
• 1976

산초수침(山椒水浸)엑기스(XW)가 가토장편(家兎腸片)에 미치는 영향(影響)은 다음과 같다. (1) XW $30\;{\mu}g/ml$ 이상(以上)은 가토장편(家兎腸片)을 수축(收縮)시켰고, (2) XW의 장수축작용(腸收縮作用)은 atropine으로 차단(遮斷)되나 hexamethonium, promethazine 및 methysergide로는 영향(影響)을 받지 않았다. 이상의 실험결과(實驗結果)는 XW가 cholinergic mechanism에 의하여 장수축(腸收縮)을 일으킴을 시사(示唆)한다.

• 대한약침학회지
• /
• 제24권4호
• /
• pp.213-213
• /
• 2021