Sustained-release Preparation Research Articles

Intracranial Drug Delivery for Subarachnoid Hemorrhage

Tice and colleagues pioneered site-specific, sustained-release drug delivery to the brain almost 30 years ago. Currently there is one drug approved for use in this manner. Clinical trials in subarachnoid hemorrhage have led to approval of nimodipine for oral and intravenous use, but other drugs, such as clazosentan, hydroxymethylglutaryl CoA reductase inhibitors (statins) and magnesium, have not shown consistent clinical efficacy. We propose that intracranial delivery of drugs such as nimodipine, formulated in sustained-release preparations, are good candidates for improving outcome after subarachnoid hemorrhage because they can be administered to patients that are already undergoing surgery and who have a self-limited condition from which full recovery is possible.

Decontamination and enhanced elimination in sustained‐release potassium chloride poisoning*

Potassium chloride poisoning can be potentially life-threatening, particularly in massive ingestions of sustained-release preparations. Profound hyperkalaemia, developing over several hours, can lead to cardiac arrhythmias and death. This case series reports three episodes of sustained-release potassium chloride poisoning in two individuals requiring whole bowel irrigation or haemodialysis. The first two episodes, in the same patient, illustrate the contrast between the successful use of decontamination versus the need for haemodialysis. The second case, in a child, illustrates the need for tertiary level paediatric expertise in managing this type of poisoning. Whole bowel irrigation with polyethylene glycol is a resource-intensive procedure most beneficial when large numbers of radio-opaque tablets are seen in the stomach. In cases where most of the tablet matter has already been absorbed, extracorporeal methods of rapidly reducing the total body burden of potassium, such as haemodialysis, might be life-saving.

Preparation and in vitro–in vivo evaluation of none gastric resident dipyridamole (DIP) sustained-release pellets with enhanced bioavailability

The objective of this study was to develop none gastric resident sustained-release pellets loaded with dipyridamole with a high bioavailability. Two different kinds of core pellets, one containing citric acid as a pH-modifier (CAP) and, the other without pH-modifier (NCAP) were prepared by extrusion-spheronization and then coated with mixtures of enteric soluble and insoluble polymers (referred to as CAP 1 and NCAP 1) or insoluble polymer alone (referred to as CAP 2 and NCAP 2). The relative bioavailability of the sustained-release pellets was studied in fasted beagle dogs after oral administration using a commercially available immediate release tablet (IRT) as a reference. The in vitro release, in vivo absorption and in vitro–in vivo correlation were also evaluated. Results revealed that the plasma drug concentrations after administration of CAP 2, NCAP 1 and NCAP 2 were undetectable, indicating that the drug release was almost zero from the preparations throughout the gastro-intestinal tract. The C max, T max and AUC (0→24) of CAP 1 were 0.78 ± 0.23 (μg/ml), 3.80 ± 0.30 (h), and 6.74 ± 0.47 (μg/ml h), respectively. While the corresponding values were 2.23 ± 0.32 (μg/ml), 3.00 ± 0.44 (h) and 9.42 ± 0.69 (μg/ml h) for IRT. The relative bioavailability of CAP 1 was 71.55% compared with IRT. By combined incorporation of a pH-modifier into the core of pellets to modify the inner micro-environment and employing mixtures of enteric soluble and insoluble polymers as a retarding layer, drugs with high solubility in stomach and limited solubility in small intestine, such as DIP, could be successfully formulated as sustained release preparations with no pH-dependence in drug release and enhanced bioavailability.

Acceleration of in vitro dissolution studies of sustained release dosage form of theophylline and in vitro–in vivo evaluations in terms of correlations

The aim of the study was to accelerate the dissolution of the sustained release dosage forms using both elevated temperature and high rpm rates. Teokap(®) SR 200 mg pellets were tested by in vitro sustained and accelerated dissolution studies using USP XXIII rotating paddle method. Sustained dissolution studies were carried out for 12 h in phosphate buffer at 37 ± 0.5°C and 50 rpm. Accelerated dissolution studies were performed for 48 min in distilled water at 90 ± 1°C and 250 rpm. The results obtained from accelerated and sustained dissolution studies were correlated using both linear and linear kinetic correlation methods by a computer program. While r (2) and maximum error between calculated and observed drug release rates were found to be 0.9129 and 15.9%, respectively, in linear correlation method, these values were observed as 0.9938 and 3.6%, respectively, in linear kinetic correlation method. In vivo plasma concentration data were obtained from six New Zealand rabbits after administration of a single dose of Teokap(®) SR 200 mg pellet. Then, the results of in vivo study were evaluated with in vitro accelerated and sustained dissolution results by applying them to in vitro-in vivo linear correlations. As a result of these correlations, it was shown that the in vitro correlation plots were very similar to the plot which was obtained by the in vivo study (f (2) = 73.81-77.11). This study suggested a way to prevent the loss of time for routine dissolution studies of sustained release preparations for quality control procedures using in vitro accelerated dissolution tests. The storage and quarantine periods of the product in process and process controls in the manufactories could be shortened by this method. Calculation of the in vivo performance of sustained release dosage forms using the results of the accelerated dissolution studies may be counted as another advantage of the method.

Sustained Release of Bone Morphogenetic Protein-4 in Adult Rabbit Extraocular Muscle Results in Decreased Force and Muscle Size: Potential for Strabismus Treatment

Purpose. To assess the effect of a sustained-release preparation of bone morphogenetic protein-4 (BMP-4) on EOM force generation and muscle size. Methods. Sustained-release pellets, releasing 500 nanograms/day of BMP-4 for a maximum of 3 months, were implanted beneath the superior rectus muscle (SR) belly in anesthetized adult rabbits. The contralateral side received a placebo pellet as a control. After 1, 3, and 6 months, SRs were removed, and force generation at twitch and tetanic frequencies as well as fatigue resistance were determined in vitro. Myofiber size, myosin heavy chain isoform expression, and satellite cell density were assessed histologically. Results. SR force generation was significantly decreased by BMP-4 compared with the contralateral controls. Force generation was decreased by 25-30% by 1 month, 31-50% by 3 months, and at 6 months, after 3 BMP-4-free months, force was still decreased by 20-31%. No change in fatigue was seen. Significant decreases in muscle size were seen, greatest at 3 months. At all time points Pax7- and MyoD-positive satellite cell densities were significantly decreased. Conclusions. The decreased force generation and muscle size caused by sustained release of BMP-4 suggests that myogenic signaling factors may provide a more biological method of decreasing muscle strength in vivo than exogenously administered toxins. Treating antagonist-agonist pairs of EOM with titratable, naturally occurring myogenic signaling and growth factors may provide safe, efficacious, nonsurgical treatment options for patients with strabismus.

The pharmacokinetics and dynamics of oxprenolol: a simulation study with six subjects.

Experimental results of plasma concentration determinations and lowering of exercise heart rate for six subjects taking a conventional tablet and a sustained release preparation of oxprenolol have been analysed by a comprehensive computer simulation model. Individual plasma values were simulated using a lest squares procedure and the results were applied to evaluate individual release patterns following dosage with the sustained release preparation. Application of the model to the lowering of exercise heart rate indicated that the response is in a steady state with the plasma values and that the response-concentration relation is of the saturable, Emax, type. The parameters for this were evaluated for each subject for the results after a dose of a conventional tablet. These parameters were applicable to the results after dosage with a sustained release preparation. The method should be applicable to other sustained release preparations.

Oral sustained-release cisplatin preparation for rats and mice.

A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II): cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios. In-vitro dissolution studies showed that cisplatin release characteristics were zero-order for the formulation cisplatin-ethylcellulose-stearic acid (1:10:5) and levels equilibrated 7 h after the start of the experiment. The availability of cisplatin from this preparation was evaluated both in rats and mice. The cisplatin preparation (20 mg kg-1) was administered orally to rats and the resulting curve of serum cisplatin levels against time was compared with that obtained after intravenous infusion (20 mg kg-1) to rats. By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%. The mean residence time (MRT) of cisplatin solid dispersion was 6.13 +/- 0.43 h, whereas the MRT of cisplatin administered by intravenous infusion was 3.89 +/- 0.05 h. Serum cisplatin levels were maintained above 0.3 mg mL-1 (believed from our clinical studies to be the minimum effective concentration) for 24 h. The curve of serum cisplatin level against time suggested that cisplatin was released from the solid dispersion preparation in a sustained-release fashion. Similar levels were also maintained in mice for 24 h. The MRT of the cisplatin preparation was 10-16 h in mice, which is longer than that obtained after oral administration of the physical mixture. The serum free-cisplatin concentration was determined to be 0.10 mg mL-1 in mice serum in which the total cisplatin concentration was 0.30 mg mL-1. The free fraction of cisplatin in mice serum was the same as that in human patient serum. Pathological examination showed that this new sustained-release oral cisplatin preparation did not have any side effects on the gastrointestinal tract. These results suggest usefulness of this new solid-dispersion preparation for oral cisplatin therapy in lung cancer patients.

Amitriptyline-Eudragit L Complex as a Sustained Release Preparation

Amitriptyline-Eudragit L Complex as a Sustained Release Preparation

Oral sustained-release cisplatin capsule.

An oral sustained-release cisplatin preparation was prepared by combining microporous water-insoluble pharmaceutical polymer, ethylcellulose, a membrane and a gel-forming polymer, poly(acrylic) acid (Carbopol). As cisplatin is an extremely hydrophilic and small compound, it was difficult to control the release rate solely by the micropores on the ethylcellulose capsule. To retain cisplatin within the capsule, gel-forming polymer was formulated inside the capsule. The release rate of cisplatin was dependent both on the number of micropores of the capsule and the formulated amount of Carbopol. The number of micropores ranged from 20 and 30 to 60, and the formulated amount of Carbopol varied from 15 to 100 mg. In-vitro release experiments suggested that the release rate decreased as the formulated amount of Carbopol increased when the pore number was 60 and 30. However, when pore number was decreased to 20, the effect of the amount of Carbopol was not clearly observed. In the in-vivo study using rabbits, the sustained-release cisplatin capsule was evaluated in comparison with solution after oral administration of 20 mg drug. With the pore number of 60, Cmax was 0.46 +/- 0.02 microgram mL-1 at 4 h and thereafter serum concentrations declined rapidly. When the pore number was 30, serum cisplatin level-time profiles showed long-acting patterns and AUC was reversely correlated with the formulated amount of Carbopol. Cmax and tmax were 0.41 +/- 0.02 microgram mL-1 and 3.33 +/- 0.88 h, respectively and 0.23 +/- 0.01 microgram mL-1 was obtained at 24 h after oral administration of capsule having 30 pores and 15 mg of Carbopol. We conclude that the possibility of developing an oral sustained-release cisplatin preparation is feasible.

An improved implantation pellet for rapid induction of morphine dependence in mice

A new type of morphine implantation pellet for the rapid induction of physical dependence in mice can be prepared by absorbing 7 mg morphine sulphate onto molecular sieves Type 4A (BDH). The small cylindrical pellets can be implanted subcutaneously without trauma and the need for anaesthesia, and are easily removed at any time from the animals. The peak of physical dependence is reached 24 h after implantation, and mortality is negligible. Withdrawal symptoms can be precipitated by intraperitoneal injection of naloxone, without removal of the pellet, and up to 70% of a group of mice show the characteristic urge to jump off a raised platform. This type of pellet has definite advantages over some other sustained-release preparations used in studies on morphine addiction in small animals.

The Coating and the Encapsulation of an Interactive Powder Mixture and its Application to Sustained Release Preparations

Fine cohesive isoprenaline HCl particles adhered to the surface of coarser potato starch particles to form interactive mixtures. These were coated with magnesium stearate by dry mixing. To check if there was a lowering of homogeneity in the latter stage, the degree of mixing was investigated before and after adding magnesium stearate. The surface appearance of magnesium stearate-coated interactive mixtures became smoother as mixing time increased or the temperature of the powder bed during mixing was raised. Ultimately, the magnesium stearate encapsulated the particles of interactive mixture. The coated interactive mixtures improved sustained release of isoprenaline HCl over the starch mixtures alone, the effect depending on the density of the magnesium stearate. Only in encapsulated mixtures was the release rate of drug decreased as the amount of magnesium stearate increased. The release of isoprenaline HCl from the interactive mixtures followed first-order kinetics. A linear relationship existed between the first-order rate constant and the reciprocal thickness of the magnesium stearate film, indicating a diffusion-controlled system with the film having some pores.

Dependence of the Renal Excretion of Theophylline on its Plasma Concentrations and Urine Flow Rate in Asthmatic Children

The dependence of the renal excretion of theophylline on its plasma concentration and urine flow rate has been investigated in asthmatic children of either sex. One group (age 12.25 +/- 0.80, mean +/- s.d. n = 8) was given aminophylline intravenously (i.v.), while another (age 10.00 +/- 3.64 n = 14) was given a sustained release preparation of theophylline orally (single dose and repeated doses). Unchanged drug (11.6% +/- 1.75) was excreted in the urine corresponding to a renal clearance of 10.6 +/- 1.6 mL h-1kg-1. Time dependence of the renal clearance of theophylline was found only after i.v. administration. Dependence of the renal clearance on urine flow rate was found both after i.v. administration and at steady state, but not after a single oral dose of theophylline. After oral administration, renal clearance of theophylline was higher at steady state than after a single dose (0.58 +/- 0.06 L h-1 kg-1 vs 0.23 +/- 0.03 L h-1 kg-1), while urine flow rate was lower (1.1 +/- 0.5 mL min-1 vs 1.8 +/- 0.9 mL min-1). High correlation of theophylline plasma concentration and theophylline excretion rate was obtained in 10 of 14 patients after administration of a single oral dose of the preparation (r = 0.8567 to 0.9830). There was no dose dependence of the renal clearance of the drug either after a single dose, or at steady state.

Use of the analogue computer to predict the distribution and excretion of drugs under conditions of fluctuating urinary pH.

Abstract An analogue computer program, incorporating a previously established relation between urinary pH and amphetamine excretion, has been used to predict the quantitative excretion of the drug under normal conditions of fluctuating urinary pH. Under the same conditions, a comparison has been made of computer predicted body levels of amphetamine after administration of the drug in a single solution dose, three divided solution doses, and in various prolonged-release formulations. Advantages of sustained-release preparations are indicated and specifications for a theoretically ideal sustained-release formulation are suggested.

A study of dimensional, swelling, and gel changes in hydrophilic and hydrophobic polymer mixtures of chitosan and their possible use as carriers for sustained release drug delivery

AbstractThe aim of this investigation was to study and estimate the dimensional changes, gel evolution, swelling, and erosion of chitosan lactate mixture tablets with Polyox or Ethocel, in distilled water and 0.1 N hydrochloric acid (HCI) solution, using an image analysis method. This method permits the accurate measurement and evaluation of dimensional changes, core changes, and gel growth. All tablets displayed greater dimensional expansion in water than in HCI. The fastest and greatest swelling was exhibited in water, whereas, in contrast, the greatest erosion was observed in HCI. Chitosan/Polyox tablets exhibited greater expansion, swelling, and gel growth than the equivalent chitosan/Ethocel tablets. The thickness of the gel layer in chitosan/Polyox tablets, particularly, increased considerably with time up to 8 h, indicating that the development of a thick and durable gel barrier is a characteristic necessity for the preparation of sustained drug release delivery systems. In addition, the differentiation of the above‐mentioned characteristics in relation to changes in pH values also gives useful information about sustained release preparations made from these polymers, since it is well known that the gastrointestinal tract is characterized by a range of pH values. In general, the polymer mixtures studied comprise a useful and promising combination of materials for the development and manufacturing of sustained release devices based on these polymers. © 2011 Wiley Periodicals, Inc. Adv Polym Techn 30: 110–121, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/adv.20208

Anti-cicatricial effect of tetrandrine drug delivery system in glaucoma filtration surgery in rabbit

Background Scarring of the filtering bleb is a main cause of filtering surgical failure in glaucoma.It has been reposed that tetrandrine could suppress the proliferation of cultured human fibroblast of Tenons capsule in vitro and thus has the potential effect to prevent scarring after the filtering surgery. Objective Present study was to investigate the anti-cicatricial effect of tetrandrine drug delivery system(Tet DDS)during filtration surgery. Methods Filtration surgery was performed in bilateral eyes of 18 New Zealand white rabbits.The Tet DDS with 0.3 mg Tet,0.2 mg Tet or free-Tet were implanted subcunjunctially during the surgery.The filtering blebs were scored in 1 day,4,7,10,14 days after referring to the corneal thickness and bleb range under the slit-lamp biomicroscopy.The morphology of filtering bleb was assessed by in vivo confocal microscopy in 7 and 14 days after operation.The filtering bleb specimen was prepared in 7 and 14 days for the histopathological examination. Results The filtering bleb scores in Tet DDS implantation groups were significantly higher than those in free-Tet DDS group from 4 days through 14 days after trabeculectomy(P＜0.01),and the scores showed a considerably increase in 0.3 mg Tet DDS group compared with 0.2 mg Tet DDS group from 7 days through 14 days after trabeculectomy(P＜0.05).The filtering blebs of Tet DDS implantation groups were found with distinct subepithelial cystic spaces under the light microscopy and in vivo confocal microscopy on the 7th day and 14th day after surgery.Compared with free-Tet DDS group,the numbers of subepithelial mierocysts were much more(P＜0.01)and the area of microcysts was larger(P＜0.01)in Tet DDS group.The filtering tissue presented with more subepithelial microcysts and larger microcysts range in 0.3 mg Tet DDS group than 0.2 mg Tet DDS group in 7 and 14 days after operation(P＜0.05).The inflammatory cell infiltration wag milder in 0.3 mg Tet DDS group in comparison with 0.2 mg Tet DDS group and free-Ted DDS group.Conclusion Tet DDS has strong inhibitory effects on inflammatory cells activity and fibroblagt activity the early stage after filtering surgery and therefore improve the surgery success rate. Key words: Tetrandrine; Sustained-release preparation; Filtration surgery; In vivo confocal microscopy; Glaucoma

Quality Assessment for Sustained Release Pharmaceutical Preparations by Dissolution Test Using Microdialysis-HPLC Method

Dissolution testing is a core performance test in pharmaceutical development and quality control. The conventional HPLC dissolution method (batch-sampling method) has many steps such as the filtration, collection and replenishment of sample solutions. We previously reported the dissolution test by using microdialysis methods (microdialysis-HPLC method) that can omit many steps. In this study, we investigated whether the microdialysis-HPLC method can be applied to quality assessment for sustained release preparations by a dissolution test. Calcium-channel blockers nifedipine tablets (20 mg) were used, and the test solution used was 0.2 M hydrogen phosphate-citric acid buffer (pH 6.8) with or without 1% sodium lauryl sulfate. In both test solutions, the microdialysis-HPLC method is able to accomplish continuous sampling of sample solutions, and the dissolution behaviors of original nifedipine tablets by the microdialysis-HPLC method were similar to that of the batch-sampling method. In contrast, the dissolution behaviors by the microdialysis-HPLC method were different between original nifedipine tablets and generic products, and the dissolution behaviors in the microdialysis-HPLC method tend to reflect the pharmaceutical design in comparison with the batch-sampling method. In addition, standard deviation in the microdialysis-HPLC method was lower than that of the batch-sampling method. We found that the recovery rate of nifedipine by the microdialysis-HPLC method was increased with the decrease in flow rate through dialysis probe. These findings provide significant information that can be used in pharmaceutical development and quality assessment for original and generic pharmaceutical products, which are sustained release preparations.

Effects of Once-Weekly Sustained-Release Growth Hormone: A Double-Blind, Placebo-Controlled Study in Adult Growth Hormone Deficiency

A sustained-release recombinant human GH formulation, LB03002, has been recently developed, with pharmacokinetics and pharmacodynamic activity appropriate for once-weekly administration. LB03002 is a long-acting GH that is administered once a week by s.c. injection. This study evaluated efficacy and safety of LB03002 in adult patients with GH deficiency. A total of 152 patients were randomized to receive LB03002 or placebo once weekly for 26 wk. Changes in body composition were evaluated from DXA (dual-energy x-ray absorptiometry). IGF-I was assessed at each study visit. Safety was assessed from adverse events, glucose homeostasis, and antibody development. IGF-I increased significantly (P < 0.001) with LB03002 and remained unchanged with placebo. Mean fat mass (FM) decreased by 1.052 kg [95% confidence interval (CI) = -1.614 to -0.491] in the LB03002 group vs. an increase of 0.570 kg (95% CI = -0.205-1.345) in the placebo group; treatment difference was 1.622 kg (95% CI = -2.527 to -0.717; P < 0.001). FM change was mainly due to decreased trunk fat. Least square mean treatment difference was 1.032 kg (95% CI = -1.560 to -0.515; P < 0.001). LBM (lean body mass) was significantly increased with LB03002 vs. placebo (least square mean difference was 1.393 kg; 95% CI = 0.614-2.171; P < 0.001). No concerning safety issues arose during the study. Weekly GH replacement with the sustained-release preparation LB03002 in adults significantly reduced FM over 6 months and was well tolerated.

Formulation and Evaluation of Sustained Release Preparation of Ibuprofen Fast-Disintegrating Tablet (FDT)

The objective of this study was to enhance the utilitization of Ibuprofen (IBU) by introducing the fast-disintegrating tablet (FDT) form. Presently, IBU is being widely used as a tablet or syrup form. But in contrast to these two formulations, IBU as FDT is not only convenient but also increases the control over the time release of the drug, noted by using Alginate beads. This study was carried out with Sodium Alginate and IBU at the ratios of 1:0, 1:0.5, 1:1, and 1:2 in order to produce a series of beads with different ratios. During the drying process of the beads, talc was added in beads to compare the effects with and without the talc. The final product was scanned with SEM imaging to determine the difference in the surface of the beads. The parameters assessed were the diameter, content assay, dissolution test and effectiveness of time-release. Direct compression method was used to prepare FDT containing IBU bead. The properties of FDT, such as hardness, disintegration time, were investigated. The dissolution profiles of FDT were tested using KP dissolution apparatus 1 (basket method). The results suggest addition of talc and drying the beads made the surface smooth and less vulnerable to clutter into chunks. The size of beads was less than 300 um which did not create a sandy feeling in the mouth. Thus, the beads formulation model made the sustained release of the drug possible, the hardness of FDT (1.25~1.50 Kg/cm2) was acceptable and all the values of dissolving period were less than 30 seconds. The dissolution profile of FDT was same as that of IBU bead. The efficient dissolution profile and low price of IBU bead containing Sodium Alginate, the FDT formulation prepared from IBU bead can save the expenses and can improve the convenience of application of this drug.

Uzefulness of the Serum 1,3-dimethyluric acid/Theophylline Concentration Ratio in Patients Treated with Sustained-release Theophylline Preparations of Various Designs

Measurement of the serum level of theophylline (TP) is essential for its appropriate use.It has been reported that the metabolic capacity of individual patients can be estimated from simultaneously measuring the serum levels of TP and these metabolites.In this study,we measured the serum TP and metabolite levels in patients treated with 2 types of sustainedrelease TP preparation,and investigated the influence of the pharmacokinetics of TP by employing different forms.The subjects were asthma patients who visited the outpatient clinic of Respiratory Medicine,St.Luke’s International Hospital,between April and October 2003,and were medicated with sustained-release TP tablets (Theodur® or Uniphyl® tablets).Blood samples were collected from patients who gave written consent.They were also interviewed and their medical records were investigated to confirm their backgrounds.The serum TP and metabolite levels were measured by HPLC.In 52 patients treated with Theodur® tablets,there was a strong correlation between the serum TP and 1,3-dimethyluric acid (DMU) levels (r=0.670).However,there was a weak correlation in 30 patients treated with Uniphyl® tablets (r= 0.249).In the two groups,the DMU/TP was within the range of the mean±SD regardless of blood collection points in all patients.The values markedly differed from this range in patients with factors influencing TP metabolism.The results suggest that,in patients receiving Theodur® tablets,their TP-metabolizing capacity can be predicted by simultaneously measuring the serum TP and metabolite levels and calculating the DMU/TP.However,such a prediction is difficult in those receiving Uniphyl® tablets.

Japanese Guideline for Adult Asthma

Adult bronchial asthma (hereinafter, asthma) is characterized by chronic airway inflammation, reversible airway narrowing, and airway hyperresponsiveness. Long-standing asthma induces airway remodeling to cause an intractable asthma. The number of patients with asthma has increased, while the number of patients who die from asthma has decreased (1.7 per 100,000 patients in 2009). The aim of asthma treatment is to enable patients with asthma to lead a healthy life without any symptoms. A partnership between physicians and patients is indispensable for appropriate treatment. Long-term management with agents and elimination of causes and risk factors are fundamental to asthma treatment. Four steps in pharmacotherapy differentiate mild to intensive treatments; each step includes an appropriate daily dose of an inhaled corticosteroid (ICS), varying from low to high doses. Long-acting β(2) agonists (LABA), leukotriene receptor antagonists, and theophylline sustained-release preparation are recommended as concomitant drugs, while anti-IgE antibody therapy is a new choice for the most severe and persistent asthma. Inhaled β(2) agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, etc., are used as needed against acute exacerbations. Allergic rhinitis, chronic obstructive pulmonary disease (COPD), aspirin induced asthma, pregnancy, and cough variant asthma are also important factors that need to be considered.