• 약학회지
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• 제44권6호
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• pp.595-600
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• 2000

Transdermal delivery of ketorolac tromethamine, a potent non-narcotic analgesic, through human cadaver skin was investigated in vitro. A mixture of ethanol/water (40/60) containing 0, 1, 3, 5, and 8 (w/v)% L-menthol were used as a vehicle and penetration enhancer respectively. The permeation of ketorolac through human cadaver skin from saturated drug solution was evaluated at $37^{\circ}C$ with modified Franz diffusion cell. The in vitro skin flux and lag time were $1.23\;{\pm}\;0.11\;{\mu}g/cm^2{\cdot}hr$ and $5.56\;{\pm}\;0.34\;hr$, respectively. The cumulative amount of penetrated ketorolac containing L-menthol in ethanol/water (40/60) binary system was increased by the following order; 3%, 5%, 8%, 1%, 0%, and the lag time was decresed by the following order; 3%, 5%, 8%, 0%, 1%. The results suggested that a potential use of 3% L-methol is an effective penetration enhancer of ketorolac tromethamine through the human cadaver skin.

• Archives of Pharmacal Research
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• 제19권6호
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• pp.529-534
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• 1996

A high-performance liquid chromatographic (HPLC) assay has been developed for the determination of ketorolac in human serum using a new extraction method with a good recovery. Human serum samples (1.0 ml) spiked with known concentrations of ketorolac tromethamine and 10${\mu}g$ of ketoprofen as the internal standard (IS) were acidified with 200${\mu}l$ of 1 N HCl and extracted with 7 ml of n-hexane-ether (7:3 v/v). Extracts were centrifuged and organic layer was back-extracted with 400${\mu}l$ of 0.1% tromethamine solution. Twenty .mu.l of centrifuged aqueous layer was injected onto a reversed-phase octyl column and eluted with a mixture of acetonitrile, water, methanol, and triethylamine [35:55:10:0.1 (v/v), pH 3.0] at a flow rate of 1.0 ml/min. Ultraviolet detection of ketorolac and IS was carried out at 300 nm. The calibration curve obtained using peak area ratios showed a good linearity (in concentration range 10-150 ng/ml $r^2$=O.9944; in range 50-2000 ng/ml, r$^{2}$=0.9998). The mean intra-day accuracy and precision for this HPLC method were found to be 3.6 and 3.7%, respectively. The mean inter-day accuracy and precision were found to be 4.0 and 3.7%, respectively, in the concentration range 50-2000 ng/ml. The recovery of ketorolac from serum was 92.0 $({\pm}5.7)$ % at the concentration of 100 ng/ml. This method proved to be readily applicable to the assay of ketorolac in human serum.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.234.1-234.1
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• 2003

The effects of vehicles and penetration enhancers on the in vitro permeation of ketorolac tromethamine (KT) across excised hairless mouse skins were investigated. Among pure vehicles examined, propylene glycol monolaurate (PGML) showed the highest permeation flux, which was 94.3${\pm}$17.3 mg/cm$^2$/hr. Even though propylene glycol monocaprylate (PGMC) alone did not show high permeation rate, the skin permeability of DT was markedly increased by the addition of diethylene glycol monoethyl ether (DGME); the enhancement factors were 19.0 and 17.1 at 20 and 40% of DGME, respectively. (omitted)

• 치위생과학회지
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• 제10권2호
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• pp.79-83
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• 2010

소염진통제인 Ketorolac tromethamine에 치자엑스 복합제제를 혼합하여 4종의 하이드로겔을 제조한 다음 주성분의 확인, 점도, 표면장력, 인장강도 및 생체부착성 실험을 통해 다음과 같은 결론을 얻었다. 1. KGE 및 KGH gel 제제 중 Ketorolac tromethamine의 함량은 1.02~0.97%이었고, Geniposide의 함량은 KGE gel A와 C에서 0.34%이었으나, KGH gel B와 D에서 0.11%로 낮아졌고, Genipin의 함량은 KGE gel A와 C에서는 나타나지 않았으나, KGH gel B와 D에서 0.13%로 나타났다. 2. Gel 제제의 온도에 따른 점도는 gel 화제로 Carbopol 940을 단독으로 사용한 gel이 Poloxamer 407을 추가한 gel보다 더 높은 점도를 유지하였으며, 각 제제에서의 표면장력은 $37^{\circ}C$에서 34.77~40.58 dyne/cm를 나타냈다. 제제의 인장강도는 KGH gel B에서 대조군에 비하여 3.5배 정도 높은 인장강도를 나타냈다. 3. 생체부착성은 등피부 상부(표피층)와 배피부의 경우 KGH gel B 에서 50.62 N으로 나타나 대조군에 비해 5배 정도 높은 수치를 나타내었고, 등피부 하부(진피층)와 배피부의 경우 KGH gel B의 에서 35.93 N으로 나타나 대조군에 비해 3.5배 정도 높은 수치를 나타냈다.

• The Korean Journal of Pain
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• 제8권1호
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• pp.37-42
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• 1995

The intermittent injection of analgesics is a inadquate method for postoperative pain control. Recently a non-electroic, disposable and portable infusor (Boxter Two Day $Infusor^R$) has been developed which can deliver analgesics with 2 ml/h speed continuousely. The present study examined the effects of three methods of pain management on recovery in 306 patients undergoing elective surgery in Wonkwang University Hospital. Group 1 (n=106) received i.m. $Valentac^R$ on a PRN basis. Group 2 (n=100), initial 2 mg of bolus morphine was followed by 48 mg of continuous infusion. Group 3 (n=100), initial 2 mg of morphine followed by morphine 18 mg-ketorolac 120 mg. We evaluated an analgesic efficacy with NRS (numerical rating scale) at 12, 24, 36, 48, 60 and 72 hours after the operation. The side effects (nausea, vomiting, pruritus, sedation and respiratory depression) were evaluated. In group 1, we asked major concern before operation and efficacy of pain control with pain severity (no pain, mild pain, moderate pain, sever pain). The results were as follows: 1) Major concern before operation is pain (40%). 2) 53% of patients suffered pain in group 1. 3) Morphine and morphine-ketorolac infusion groups were superior to the i. m. ($Valentac^R$) group with respect to postoperative analgesia. 4) In group 3 (morphine-ketorolac), there was no pruritus and mild nausea and vomiting.

• Journal of Pharmaceutical Investigation
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• 제33권1호
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• pp.21-28
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• 2003

Ketorolac tromethamine(KT) is a nonsteroidal agent with potent analgesic and moderate anti-inflammatory activity. The lipid-water partition coefficient of KT was evaluated and KT gel was formulated as a gel containing different pH, different concentrations of polymer (poloxamer 407, carbopol 941), propylene glycol, ethanol and various enhancers. The resulting KT gels were evaluated with respect to their viscosity, in vitro drug permeation rate through hairless mouse skin and stability. In n-octanol and chloroform, the lipid-water partition coefficient of KT was the highest at pH 4 phosphate buffer. The apparent viscosity of KT gel increased with an increase in gel pH, polymer and enhancer concentration. But the apparent viscosity of KT gel decreased with an increase in ethanol concentration. The permeation rate of KT through hairless mouse skin from gels different pH was maximum at pH 4 which is close to KT $pK_{a}$ 3.54. The permeation rate decreased with an increase in polymer, propylene glycol concentration. But the permeation rate increased with an increase in ethanol. The increase of drug concentration from 1 to 3% induced linear increase in permeation rate. The best enhancer was the combination of $Labrasol^{\circledR},\;Transcutol^{\circledR}$, oleic acid and l-menthol. In the accelerated stability test(25, 40 and $50{\circ}C$), pH 5 gel was most stable and pH 4 gel was most unstable for 90 days.

• Journal of Pharmaceutical Investigation
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• 제29권1호
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• pp.67-72
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• 1999

A bioequivalence study of the $Kerola^{\circledR}$ intramuscular injections (Dongkwang Pharmaceutical Co., Korea) to the $Tarasyn^{\circledR}$ intramuscular injections (Roche Co., Korea), formulations of ketorolac tromethamine (KTR), was conducted. Sixteen healthy Korean male subjects were received each formulation at the dose of 30 mg as KTR in a $2{\times}2$ crossover study. There was an one-week washout period between the doses. Plasma concentrations of KTR were monitored by a HPLC method. AUC was calculated by the linear trapezoidal method. $C_{max}$ and $T_{max}$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The differences between the formulations in these parameters were all far less than 20% (i.e., 3.65, 2.59 and 4.35% for AUC, $C_{max}$ and $T_{max}$ respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were 12.87, 13.44, 20.62%, for AUC, $C_{max}$ and $T_{max}$, respectively. The 90% confidence intervals for these parameters were also within 20%. These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 1998-86). Therefore, these results indicate that the two formulations of KTR are bioequivalent.

• 치위생과학회지
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• 제5권3호
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• pp.113-117
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• 2005

소염진통제인 케토롤락트로메타민에 치자엑스 복합제제를 혼합하여 4종의 하이드로겔 제제를 제조한 후 인장강도측정, 피부투과 및 치주낭 감소율측정 실험을 통해 다음과 같은 결론을 얻었다. 1. 제제의 인장강도는 KGH gel B에서 대조군에 비하여 3.5배 정도 높은 인장강도를 나타내었다. 2. 케토롤락트로메타민의 피부투과량은 8시간 동안 KGH gel B에서 $105.62{\mu}m/cm^2$로 가장 높았고, geniposide 투과량은 KGE gel A에서 $73.8{\mu}m/cm^2$ 비교적 높았으나 가수분해물인 genipin의 투과량은 KGH gel B에서$50.17{\mu}m/cm^2$ 가장 높은 투과량을 나타내었다. 3. 치주낭 감소율은 4주 후 KGE gel A는 대조군에 비하여 23.85%의 감소율을 나타내었으나 유의성 있는 차이는 나타내지 못하였으며, KGH gel B는 대조군에 비하여 29.46%의 감소율을 보여 유의성 있는 치료효과를 나타내었다.

• Journal of Pharmaceutical Investigation
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• 제30권4호
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• pp.241-246
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• 2000

To develop a sustained-release preparation containing ketorolac tromethamine, two sustained-release pellet formulations were evaluated with a pharmacokinetic study as compared with a conventional commercial tablets (10 mg $Tarasyn^{TM}$, Roche Korea Ltd.). Two sustained-release formulations were as follows; formulation A was composed of an inner layer containing 75% of drug coated with $Eudragit^{TM}$ RS 100 membrane and an outer layer containing 25% of drug mixed with $Eudragit^{TM}$ NE30D, and formulation B was composed of only an inner layer containing 100% of drug coated with $Eudragit^{TM}$ RS 100 membrane. The dissolution test was performed for two formulations. In case of conventional tablets, 2.5 mg of drug per a dose was administered orally into male Albino rabbit (2.0-2.3 kg of body weight) 3 times at intervals of 4 hours. In case of two sustained formulations, 7.5 mg of drug was administered once orally. Blood samples were withdrawn periodically after the administration, and the blood concentration was determined by HPLC. The conventional tablets showed very high peak-trough fluctuation between administered doses, but two sustained formulations showed less fluctuation. Formulation A with the loading dose showed the time to reach minimum effective concentration (MEC) i.e. the onset time was less than 20 min, while Formulation B had more than 1 hr of the onset time. Formulation A had the more constant plasma level than formulation B. However, formulation B had a time lag, so the plasma level was less than MEC for an initial period of 1 hr. In formulation A, the plasma level was maintained within the therapeutic window $(0.3-5\;{\mu}g/ml)$ for a long period. Formulation A was thought to be an ideal sustained-release formulation for ketorolac tromethamine oral delivery system.

• 대한두경부종양학회지
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• 제16권2호
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• pp.182-186
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• 2000

The reduction of the postoperative wound pain has been a concern in recent surgery, especially in various types of minimally-invasive surgeries. This study was performed to evaluate the postoperative analgesic effect of the preincisional local anesthesia with the mixture of ketorolac(Tarasyn) and bupivacaine to the surgical site in minimally-invasive thyroid surgeries. Of 491 patients who were scheduled for minimally-invasive thyroid surgeries between October 1999 and July 2000, 244 were randomly assigned to receive a mixture of ketorolac tromethamine 15mg(0.5ml) and 0.25% bupivacaine 3ml via surgical site infiltration 3 minutes prior to the skin incision. The outcomes of these patients were compared to those of the 247 controls. Total number of patients in need of post-operative analgesic requirements(n=39, 16.0%), total dose of postoperative analgesics used($19.6{\pm}8.4mg$ of ketorolac) and Visual Analogue Pain Score(VAS, $2.6{\pm}1.2$) of the preincisional local anesthesia group were significantly lower than those of the control group(p<0.05). The mean postoperative hospital stay was $1.6{\pm}0.4$ days for the preincisional local anesthesia group versus $1.9{\pm}0.7$ days for the control group. The preincisional local infiltration of ketorolac and bupivacaine in the minimally invasive thyroidectomies reduces postoperative wound pain thus would be more beneficial to the patients.