• Journal of Pharmaceutical Investigation
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• 제36권3호
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• pp.157-160
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• 2006

This study investigated the effect of clarithromycin on the pharmacokinetics of ambroxol in rats. The pharmacokinetic parameters of ambroxol in rats were determined after the oral administration of ambroxol (12 mg/kg) in the presence or absence of clarithromycin (5 or 10 mg/kg). Compared with the control (given ambroxol alone), coadministration of clarithromycin significantly (p<0.05 at 5 mg/kg; p<0.01 at 10 mg/kg) increased the area under the plasma concentration-time curve (AUC), peak plasma concentrations $(C_{max})$ and absorption rate constant $(K_a)$ of ambroxol. Clarithromycin increased the AUC of ambroxol in a dose dependent manner within the dose range of 5 to 10 mg/kg. The absolute bioavailability (AB%) of ambroxol in the presence of clarithromycin was significantly higher than that of the control (p<0.05 at 5 mg/kg; p<0.01 at 10 mg/kg), and the relative bioavailability (RB%) of ambroxol with clarithromycin was increased by 1.32-to 1.71-fold. However, there were no significant changes in time to reach peak concentration $(T_{max})$ and terminal half-life $(T_{1/2})$ of ambroxol in the presence of clarithromycin. Coadministration of clarithromycin enhanced the bioavailability of ambroxol, which may be due to the inhibition of intestinal and hepatic metabolism of ambroxol by CYP 3A4. Further studies for the potential drug interaction are necessary since ambroxol is often administrated concomitantly with clarithromycin in humans.

• Journal of Yeungnam Medical Science
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• 제16권1호
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• pp.52-59
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• 1999

미숙아의 여러 가지 합병증 중에서도 선생아 호흡 곤란 증후군은 가장 빈도가 높고 사망률도 높은 질병이다. 이제까지 많은 저자들이 자궁내 성장기 동안에 폐 표면 활성제 생성을 증가시킴으로써 신생아 호흡 곤란 증후군을 예방할 수 있는 약제로 corticosteroid에 대한 연구를 하였으나, 산모와 태아 감염에 중요한 위협 요인이 되어 이 약의 사용이 제한적이다. 따라서 steroid의 부작용 때문에 태아의 폐를 성숙시킬 수 있는 ambroxol에 관심을 가지게 되었으며 이에 저자들은 출생 전 산모에게 투여한 ambroxol이 신생아 호흡 곤란 증후군의 발생 빈도에 어떤 영향을 미치는지와 그 부작용에 대해 알아보고자 하였다. 1996년 1월부터 1997년 12월까지 영남대학교 의과대학 부속 병원 산부인과에 입원하였던 36주 이전의 조산이 예견된 산모에게 ambroxol(Mucosolvan$^{(R)}$, Boehringer Ingelheim) 1,000mg을 5% glucose 용액에 녹여 2시간 이상 정주하며 3일에서 5일간 투여하였다. 또한 대조군에서는 생리 식염수를 정주하였다. 조기 분만의 원인이나 대상 환아 평균 재태 연령, 남녀비, 출생 체중과 1, 5분 Apgar 점수가 7점 미만인 미숙아의 수에는 양 군간의 의미있는 차이는 없었다. 그러나 대조군에서는 21명 중 13명에서 신생아 호흡 곤란 증후군이 발생하였고 ambroxol 사용군에서는 21명 중 6명에서 신생아 호흡 곤란 증후군이 발생하여 두 군간에 의미있는 차이가 있었다(p<0.05). 출생 후 산소 치료와 인공 환기를 필요로 했던 경우는 대조군에서는 각각 18, 12명이었고 ambroxol 사용군에서는 각각 9, 8명이었다. 산소치료를 요구된 시간은 ambroxol 군에서 낮았으나 인공 환기가 필요하였던 시간은 ambroxol 군에서 더 길었다. 그 외 미숙아에게 나타난 주산기 합병증의 빈도는 ambroxol 사용군과 대조군을 비교해 보면 두 군이 같거나 ambroxol 군이 더 적었다. Ambroxol 투여 전과 후의 산모의 혈액학적, 생화학적 검사에 의미있는 변화는 없었다. 그리고 ambroxol 사용군에서 산모가 호소하는 부작용으로는 경미한 오심이 3례 있었으나 구토, 두통이나 현기증, 알레르기 반응 등은 나타나지 않았다. 그러므로 본 연구에서는 미숙아 출생 전 산모에게 투여한 ambroxol은 신생아 호흡 곤란 증후군의 발생 빈도를 감소시킨다고 생각되며 이를 위해 산모에게 안전하게 사용할 수 있는 약제로 생각된다.

• Biomolecules & Therapeutics
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• 제6권2호
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• pp.111-118
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• 1998

Ambroxol is thought to have antioxidant ability and some antiinflammatory effect. Effect of ambroxol on the oxidative damages of lipid, collagen and hyaluronic acid was examined. F $e_{2+}$(10 $\mu$M) and 100$\mu$Mascorbate-induced lipid peroxidation of liver microsomes was inhibited by 10 and 100$\mu$M ambroxol, 30$\mu$g/ml catalase and 10 mM DABCO but was not affected by 30$\mu$g/ml SOD and 10 mM DMSO. A 10 and 100$\mu$M ambroxol and 10 mM DABCO inhibited the peroxidative action of 10$\mu$M F $e_{3+}$, 160$\mu$M ADP and 100$\mu$M NADPH on microsomal lipids, whereas inhibitory effects of 30$\mu$g/ml SOD,30$\mu$g/ml catalase and 10 mM DMSO were not detected. The degradation of hyaluronic acid caused by 107M Fe2\\`,5007M H2O2 and 100$\mu$M ascorbate was inhibited by 10 and 100$\mu$M ambroxol,30$\mu$g/ml catalase,10 mM DMSO and 10 mM DABCO, while 30$\mu$g/ml SOD did not show any effect. The cartilage collagen degradation caused by 307$\mu$ F $e_{2+}$,500$\mu$M $H_2O$$_2$ and 200$\mu$M ascorbate was prevented by 100$\mu$M ambroxol. $H_2O$$_2$ and OH . were scavenged by ambroxol, whereas $O_2$, was not removed by it. Ambroxol (100$\mu$M) and 1 mM cysteine reduced DPPH to 1,1-diphenyl-2-picrylhydrazine. In conclusion, ambroxol may inhibit the oxidative damages of lipid, hyaluronic acid and collagen by its scavenging action on oxidants, such as OH . and probably iron-oxygen complexes and exert antioxidant ability.

• 대한화학회지
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• 제52권6호
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• pp.622-629
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• 2008

• Biomolecules & Therapeutics
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• 제7권2호
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• pp.112-120
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• 1999

The protective actions of ambroxol, rutin, glutathione and harmaline on oxidative damages of various tissue components were compared. The mechanisms by which they prevent oxidative tissue damages were explored. Lipid peroxidation of liver microsomes induced by combinations of $Fe^{2+}$ and ascorbate or $Fe^{+3}$, ADP and NADPH was inhibited by $50\; \muM$ of rutin, ambroxol, harmaline and glutathione. Ambroxol ($100\; \muM$) inhibited the degradation of hyaluronic acid by $Fe^{2+}$, $H_2O$_2$ and ascorbate, and it was greater than that of harmaline, whereas hyaluronic acid degradation was not prevented by rutin and glutathione. The compounds used ($100\; \muM$) did not protect the degradation of cartilage collagen by xanthine and xanthine oxidase. Rutin, glutathione and harmaline decreased the degradation of IgG by xanthine and xanthine oxidate, while ambroxol did not attenuate degradation of IgG. Glutathione showed a scavenging action on $H_2O_2$. The compounds all showed scavenging actions on hydroxyl radical. Ambroxol and harmaline exhibited quenching effects en singlet oxygen. In conclusion, ambroxol, rutin, glutathione and harmaline may exert protective effects differently on tissue components against oxidative attack depend on kind of tissue component and free radical.

• Biomolecules & Therapeutics
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• 제18권1호
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• pp.106-110
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• 2010

The pharmacokinetics and bioavailability of ambroxol, an expectoration improver and mucolytic agent, were studied to determine the feasibility of enhanced transdermal delivery of ambroxol from the ethylene-vinyl acetate (EVA) matrix system containing polyoxyethylene-2-oleyl ether as an enhancer in rats. The ambroxol-010 matrix system (15 mg/kg) was applied to abdominal skin of rats. Blood samples were collected via the femoral artery for 28 hrs and the plasma concentrations of ambroxol were determined by HPLC. Pharmacokinetic parameters were calculated using Lagran method computer program. The area under the curve (AUC) was significantly higher in the enhancer group ($1,678{\pm}1,413.3\;ng/ml{\cdot}hr$) than that in the control group $1,112{\pm}279\;ng/ml{\cdot}hr$), that is treated transdermally without enhancer, showing about 151% increased bioavailability (p<0.05). The average $C_{max}$ was increased in the enhancer group ($86.0{\pm}21.5\;ng$/ml) compared with the control group ($59.0{\pm}14.8\;ng$/ml). The absolute bioavailability was 13.9% in the transdermal control group, 21.1% in the transdermal enhancer group and 18.1% in the oral administration group compared with the IV group. The $T_{max}$, $K_a$, MRT and $t_{1/2}$ of ambroxol in transdermal enhancer group were increased significantly (p<0.01) compared to those of oral administration. As the ambroxol-EVA matrix containing polyoxyethylene-2-oleyl ether and tributyl citrate was administered to rats via the transdermal routes, the relative bioavailability increased about 1.51-fold compared to the control group, showing a relatively constant, sustained blood concentration. The results of this study show that ambroxol-EVA matrix could be developed as a transdermal delivery system providing sustained plasma concentration.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.65-69
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• 2011

In this study, we investigated whether ambroxol significantly affects secretion, production and gene expression of mucin from cultured airway epithelial cells. Confluent primary rat tracheal surface epithelial (RTSE) cells were pretreated with adenosine triphosphate (ATP) for 5 min and then treated for 30 min with ambroxol to assess the effect on mucin secretion using ELISA. Additionally, confluent NCI-H292 cells were pretreated with ambroxol for 30 min and then stimulated with EGF or PMA for 24 h. The MUC5AC mucin gene expression and mucin protein production were measured by RT-PCR and ELISA. The results were as follows: (1) ambroxol did not significantly affect ATP-induced mucin secretion from cultured RTSE cells; (2) ambroxol inhibited the production of MUC5AC mucin protein induced by EGF and PMA in NCI-H292 cells; (3) ambroxol also inhibited the expression of MUC5AC mucin gene induced by EGF and PMA in NCI-H292 cells. This result suggests that ambroxol can inhibit the production and gene expression of MUC5AC mucin, by directly acting on human airway epithelial cells.

• IMMUNE NETWORK
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• 제16권3호
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• pp.165-175
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• 2016

Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.279.1-279.1
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• 2003

NIR reflectance spectroscopy, using a fiber-optic probe was used to determine rapidly and non-destructively the content of ambroxol in intact ambroxol 30 mg (nominal content 12.5％ m/m ambroxol) tablets by collecting NIR spectra in range 1100 - 1750 nm and using PLSR calibration method. The tablets (10.3 - 15.9％ m/m ambroxol, i.e., 82 - 127％ of the nominal label content) were used 7 calibration set and 5 validation set. (omitted)

• 약학회지
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• 제57권3호
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• pp.194-198
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• 2013

In the present study we evaluated drug-drug interaction potential of ambroxol and cetirizine mediated by inhibition of CYP isoforms including CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 using pooled human liver microsomes (HLMs). As measured by liquid chromatography-electrospray ionization tandem mass spectrometry, cetirizine and ambroxol inhibited significantly CYP2E1 but the maximal inhibition was approximately 36% at 10 ${\mu}M$ cetirizine and 28% at 3 ${\mu}M$ ambroxol. In addition, CYP2D6 activity was decreased to approximately 83% of control activity in pooled HLM incubated with 3 ${\mu}M$ ambroxol. Activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 were not significantly inhibited by cetirizine and ambroxol. Considering their maximal plasma concentration in human ($C_{max}$ of cetirizine is approximately 0.67 ${\mu}M$ and $C_{max}$ of ambroxol is 0.044 ${\mu}M$), these two drugs have very low possibility in drug-drug interaction by CYP inhibition in clinical situations.