Hydrochloride Combination Research Articles

Validated Simultaneous UV Spectrophotometric Methods for estimation of Tramadol Hydrochloride and ketorolac Tromethamine in bulk and marketed Capsule Formulation

The present study describes new, simple, rapid and novel spectrophotometric methods for simultaneous estimation of Tramadol Hydrochloride and Ketorolac Tromethamine combination was analysed by simultaneous equation method (Method B) and First order derivative spectroscopic method (Method C). Method A involved measurement of absorbance at two wavelengths, 271 nm and 246 nm, λmax of tromethamine respectively. For method B, wavelengths 331 nm (for determination of Ketorolac tromethamine) and 271 nm were used. For method C, wavelengths 339.2 nm (Zero crossing of Tramadol hydrochloride) and 229.4 nm (Zero crossing of Ketorolac tromethamine) were used for determination of Ketorolac tromethamine and Tramadol hydrochloride respectively. Beer's law was obeyed in concentration range of 5–50 μg/ml and 2–20 μg/ml for Tramadol hydrochloride and Ketorolac tromethamine respectively by all the methods. Method C was found to be more simple and sensitive. The proposed methods are pharmaceutical formulations due to their specificity, rapidity, simplicity and accuracy. These methods validated for linearity, accuracy and precision as per ICH guidelines.

Effect of dexmedetomidine hydrochloride on tiletamine hydrochloride-zolazepam hydrochloride anesthesia in alpacas.

OBJECTIVE To evaluate the effect of IM administration of a tiletamine hydrochloride-zolazepam hydrochloride (TZ) combination with either dexmedetomidine hydrochloride or saline (0.9% NaCl) solution (SS) on the motor response to claw clamping, selected cardiorespiratory variables, and quality of recovery from anesthesia in alpacas. ANIMALS 5 adult sexually intact male alpacas. PROCEDURES Each alpaca was given the TZ combination (2 mg/kg) with dexmedetomidine (5 [D5], 10 [D10], 15 [D15], or 20 [D20] µg/kg) or SS IM at 1-week intervals (5 experiments); motor response to claw clamping was assessed, and characteristics of anesthesia, recovery from anesthesia, and selected cardiorespiratory variables were recorded. RESULTS Mean ± SEM duration of lack of motor response to claw clamping was longest when alpacas received treatments D15 (30.9 ± 5.9 minutes) and D20 (40.8 ± 5.9 minutes). Duration of lateral recumbency was significantly longer with dexmedetomidine administration. The longest time (81.3 ± 10.4 minutes) to standing was observed when alpacas received treatment D20. Following treatment SS, 4 alpacas moved in response to claw clamping at the 5-minute time point. Heart rate decreased from pretreatment values in all alpacas when dexmedetomidine was administered. Treatments D10, D15, and D20 decreased Pao2, compared with treatment SS, during the first 15 minutes. During recovery, muscle stiffness and multiple efforts to regain a sternal position were observed in 3 SS-treated and 1 D5-treated alpacas; all other recoveries were graded as excellent. CONCLUSIONS AND CLINICAL RELEVANCE In TZ-anesthetized alpacas, dexmedetomidine (10, 15, and 20 µg/kg) administered IM increased the duration of lack of motor response to claw clamping, compared with the effect of SS.

Application of fast-track surgery principles to evaluate effects of atipamezole on recovery and analgesia following ovariohysterectomy in cats anesthetized with dexmedetomidine-ketamine-hydromorphone.

To evaluate the effects of atipamezole hydrochloride on recovery and analgesia following ovariohysterectomy in cats anesthetized with a dexmedetomidine hydrochloride, ketamine hydrochloride, and hydromorphone hydrochloride combination, in accordance with fast-track surgery principles. Prospective, randomized, clinical trial. 44 cats. Cats were anesthetized with a combination of dexmedetomidine (15 μg/kg [6.8 μg/lb]), ketamine (5 mg/kg [2.3 mg/lb]), and hydromorphone (0.05 mg/kg [0.023 mg/lb]), IM, supplemented with isoflurane in oxygen. Immediately after ovariohysterectomy, cats received meloxicam (0.2 mg/kg [0.09 mg/lb]) SC and either atipamezole (75 μg/kg [34.1 μg/lb]) or an equivalent volume of saline (0.9% NaCl) solution IM. Pain and sedation were scored at baseline (prior to surgery) and at predetermined intervals after surgery. Time to sternal recumbency was recorded. The atipamezole group recovered to sternal recumbency faster (median, 15 minutes; range, 5 to 60 minutes) than the saline solution group (median, 60 minutes; range, 15 to 90 minutes]). Pain scores did not differ between groups or at any time, compared with baseline, and were below the intervention threshold for most cats. Sedation scores were significantly greater in the saline solution group (median, 0; range, 0 to 2) at 2 hours after surgery, compared with the atipamezole group (median, 0; range, 0 to 0). Results indicated that administration of atipamezole, compared with saline solution, allowed for a faster recovery from anesthesia with dexmedetomidine-ketamine-hydromorphone in cats following ovariohysterectomy without compromising analgesia. These findings have implications for the provision of appropriate postoperative analgesia following ovariohysterectomy in cats.

Functional synergy of α-helical antimicrobial peptides and traditional antibiotics against Gram-negative and Gram-positive bacteria in vitro and in vivo.

In this study, the antimicrobial activities based on the synergistic effects of traditional antibiotics (imipenem, cefepime, levofloxacin hydrochloride and vancomycin) and antimicrobial peptides (AMPs; PL-5, PL-31, PL-32, PL-18, PL-29 and PL-26), alone or in combination, against three Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae and Staphylococcus epidermidis) and three Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae) were investigated. In addition, the antimicrobial activity that was based on the synergistic effects of levofloxacin hydrochloride and PL-5 against Staphylococcus aureus in vivo was explored in a mouse infection model. Traditional antibiotics and AMPs showed significant synergistic effects on the antibacterial activities against the different Gram-positive and Gram-negative bacteria in vitro. A strong synergistic effect in the PL-5 and levofloxacin hydrochloride combination against Staphylococcus aureus was observed in the mouse infection model in vivo. The mechanism of synergistic action was due to the different targets of AMPs and traditional antibiotics. The combination of AMPs and traditional antibiotics can dramatically enhance antimicrobial activity and may help prevent or delay the emergence of antibiotic resistance. Thus, this combination therapy could be a promising approach to treat bacterial infections, particularly mixed infections and multi-antibiotic-resistant infections, in the clinics.

Method development and validation of chlordiazepoxide and amitryptyline hydrochloride in pharmaceutical formulations by RP-HPLC

A simple, precise and rapid, reversed phase-high performance liquid chromatography (RP-HPLC) method is developed for simultaneous determination of chlordiazepoxide and amitriptyline hydrochloride in tablet dosage forms. The HPLC conditions used are methanol: acetonitrile (75:25 v/v) mobile phase, Zodiac C18 column (250mm x 4.6mm x 5μm), pump pressure (9.5 MPa) and detection wavelength (221 nm). The measured elution times are 4.87±0.02 minutes for chlordiazepoxide and 7.38±0.02 minutes for amitriptyline hydrochloride, respectively. The method is validated for linearity range, recovery, robustness and sensitivity. Linearity is demonstrated for chlordiazepoxide and amitriptyline hydrochloride in the range 5-30 μg/mL (r2 = 0.9998) and 15-75 μg/ml (r2 = 0.9997). The mean recoveries ranged from 98.81-100.63% and 98.97-101.33% and the limit of detections (LOD) are 0.15 μg/ml and 0.5 μg/ml for chlordiazepoxide and amitriptyline hydrochloride, respectively. The proposed method proved to be specific, robust and accurate and has good signal to noise ratio with well resolved peaks for unambiguous determination of chlordiazepoxide and amitriptyline hydrochloride combination and in tablet dosage form.

顎関節症・咀嚼筋痛障害に伴う慢性疼痛へのトラマドール塩酸塩/アセトアミノフェン配合錠の使用経験

顎関節症・咀嚼筋痛障害に伴う慢性疼痛へのトラマドール塩酸塩/アセトアミノフェン配合錠の使用経験

Pharmaceutical quality of seven generic Levodopa/Benserazide products compared with original Madopar® / Prolopa®

BackgroundBy definition, a generic product is considered interchangeable with the innovator brand product. Controversy exists about interchangeability, and attention is predominantly directed to contaminants. In particular for chronic, degenerative conditions such as in Parkinson’s disease (PD) generic substitution remains debated among physicians, patients and pharmacists. The objective of this study was to compare the pharmaceutical quality of seven generic levodopa/benserazide hydrochloride combination products marketed in Germany with the original product (Madopar® / Prolopa® 125, Roche, Switzerland) in order to evaluate the potential impact of Madopar® generics versus branded products for PD patients and clinicians.MethodsMadopar® / Prolopa® 125 tablets and capsules were used as reference material. The generic products tested (all 100 mg/25 mg formulations) included four tablet and three capsule formulations. Colour, appearance of powder (capsules), disintegration and dissolution, mass of tablets and fill mass of capsules, content, identity and amounts of impurities were assessed along with standard physical and chemical laboratory tests developed and routinely practiced at Roche facilities. Results were compared to the original “shelf-life” specifications in use by Roche.ResultsEach of the seven generic products had one or two parameters outside the specifications. Deviations for the active ingredients ranged from +8.4% (benserazide) to −7.6% (levodopa) in two tablet formulations. Degradation products were measured in marked excess (+26.5%) in one capsule formulation. Disintegration time and dissolution for levodopa and benserazide hydrochloride at 30 min were within specifications for all seven generic samples analysed, however with some outliers.ConclusionsDeviations for the active ingredients may go unnoticed by a new user of the generic product, but may entail clinical consequences when switching from original to generic during a long-term therapy. Degradation products may pose a safety concern. Our results should prompt caution when prescribing a generic of Madopar®/Prolopa®, and also invite to further investigations in view of a more comprehensive approach, both pharmaceutical and clinical.

Nedaplatin and irinotecan combination therapy is equally effective and less toxic than cisplatin and irinotecan for patients with primary clear cell adenocarcinoma of the ovary and recurrent ovarian carcinoma

This study retrospectively compared nedaplatin and irinotecan hydrochloride (NDP/CPT) combination therapy with cisplatin and irinotecan hydrochloride therapy (CDDP/CPT) for efficacy and adverse events in the treatment of clear cell adenocarcinoma of the ovary (CCC) and recurrent ovarian carcinoma. A total of 115 patients were included in the present study. NDP/CPT was administered intravenously every 4 weeks (NDP, 60 mg/m(2) on day 1; CPT, 50 mg/m(2) on days 1, 8 and 15). CDDP/CPT was also administered intravenously (CDDP, 60 mg/m(2) on day 1; CPT, 60 mg/m(2) on days 1, 8 and 15). Patients with primary CCC were treated with NDP/CPT in 29 cases and CDDP/CPT in 20 cases. Patients with recurrent ovarian carcinoma were treated with NDP/CPT and CDDP/CPT in 33 cases each. No significant difference was observed in the 5-year overall survival (OS)/progression-free survival (PFS) of patients with primary CCC, with the exception of those patients with stages Ia and Ic(b) who underwent NDP/CPT and CDDP/CPT treatments (OS: 58%, PFS: 40% and OS: 53% and PFS: 47%, respectively). No significant differences were found in the response rates to NDP/CPT and CDDP/CPT in patients with recurrent ovarian carcinoma (27 and 18%, respectively). Similarly, there were no significant differences in the 5-year OS and PFS of patients with recurrent ovarian carcinoma treated with NDP/CPT or CDDP/CPT (OS: 15%, PFS: 3% and OS: 18%, PFS: 6%, respectively). In terms of the hematological toxicity of grade 3 or above and non-hematological toxicity of grade 2 or above in patients treated with NDP/CPT and CDDP/CPT, respectively, neutropenia was 23 and 56%; anemia, 1, and 20%; thrombocytopenia, 0 and 5%; nausea, 20 and 52%; diarrhea, 14 and 25%; and fever, 2 and 11%. Accordingly, NDP/CPT indicated mild toxicity, and was therefore equally effective and less toxic than CDDP/CPT in the treatment of primary CCC and recurrent ovarian carcinoma.

Combination Effects of the Antimicrobial Agents and Cinnamon Oil

The use of antimicrobial combination may be interesting because it can decrease doses and side effects of antimicrobial agents. The cinnamon essential oil was examined with respect to antimicrobial modifying activity. The combination effect of antimicrobial agents (doxycycline hyclate, ciprofloxacin HCl and metronidazole) and cinnamon oil was evaluated by checkerboard method to obtain a fractional inhibitory concentration (FIC) index. The effect of metronidazole+doxycycline hyclate and metronidazole+ciprofloxacin hydrochloride combinations were additive against Staphylococcus aureus. The indifference FIC index was observed only with the doxycycline hyclate+ciprofloxacin HCl combination. Combinations of cinnamon oil and all antimicrobial agents showed the additive effects against S. aureus. These results indicated that the antimicrobial activity of cinnamon oil was generally additive to all test antimicrobial agents.

Systemic Bioavailability and Pharmacokinetics of the Doxylamine–Pyridoxine Delayed-Release Combination (Diclectin)

Diclectin, composed of 10 mg doxylamine succinate (DOX) and 10 mg pyridoxine hydrochloride, is the drug combination of choice for the management of nausea and vomiting during pregnancy in Canada. However, there is large variability in its onset and duration of action among women. To understand and improve its effectiveness, the variability in the pharmacokinetics of the ingredients in this doxylamine succinate/pyridoxine hydrochloride combination must be studied. To determine the pharmacokinetics of DOX and pyridoxine after oral administration of two tablets of this drug combination in the form of Diclectin and to calculate their respective relative bioavailability by comparison with intravenous administration in another population. Eighteen nonpregnant, nonlactating, healthy females between 18 and 45 years of age were administered two tablets of Diclectin with 240 mL of water under empty stomach conditions. Blood samples were analyzed for DOX and pyridoxine along with its four active metabolites: pyridoxal, pyridoxal-5'-phosphate (PLP), pyridoxamine, and pyridoxamine-5'-phosphate using tandem mass spectrometry. For the purpose of this study, pharmacokinetic values for DOX and PLP were adjusted for body weight. The mean DOX-AUC0→∞ was calculated to be 3137.22 ± 633.57 ng·hr/mL (range, 2056.59-4376.06 ng·hr/mL). The mean PLP-AUC0→∞ was calculated to be 5513.10 ± 2362.35 ng·hr/mL (range, 1572.56-10,153.77 ng·hr/mL). Based on literature values of the PLP-AUC0→∞ after intravenous administration and data from the current study, the relative bioavailability of pyridoxine in Diclectin was calculated at 100%. There was a 2.1-fold variability in the DOX-AUC0→∞ and 6.5-fold variability in the PLP-AUC0→∞ after oral administration of 20 mg Diclectin. Using literature values and data from the current study, we estimated the oral bioavailability of pyridoxine to be 100%. Therefore, interindividual differences in metabolism, and not in bioavailability, may be important sources of variability that need to be addressed in dosing guidelines.

Treatment of Uncomplicated Falciparum Malaria with Artesunate-Amodiaquine Combination Therapy (ACT) in a Rural Fishing Community in Sierra Leone

Until recently, Chloroquine was the mainstay for malaria chemotherapy in Africa because it is cheap, safe and practicable for out-patient use. Resistance to this drug has however over the past decade, presented a major public health problem with therapeutic and prophylactic implications. As a response to the emergence of resistance to the commonly used antimalarial drugs, the World Health Organisation (WHO) now recommends the use of artemisinin-based combination therapies (ACTs). We assessed the therapeutic efficacy of oral Artesunate-Amodiaquine hydrochloride combination therapy in the treatment of uncomplicated falciparum malaria in a rural fishing community in Sierra Leone. One hundred and fourteen (114) participants aged 0 – 5 years attending the Outpatient Department of Gbondapi Health Centre were screened for recruitment into the study of which 70 fulfilled the inclusion criteria. Artesunate-Amodiaquine hydrochloride combined drug which passed the general counterfeit test of the Ministry of Health and Sanitation was used in the study. Adequate Clinical and parasitological Response (ACPR) was observed in 97% of the study population. Mean parasite clearance time in the participants with ACPR was found to be 24 hours (range 24 –72 hours). All 3% of the treatment failures were observed to be Early Treatment Failures (ETF). Results from the study indicate that Artesunate-Amodiaquine hydrochloride combination therapy is an effective antimalarial drug in a high transmission zone like Sierra Leone, and in the event that the drug is not effective, the results will be evident within one day of commencement of treatment.

Granuloma Annulare Treated With Rifampin, Ofloxacin, and Minocycline Combination Therapy

Granuloma annulare (GA) is a benign, usually self-limiting, dermatosis, that typically presents as asymptomatic, flesh-colored or erythematous papules, frequently arranged in an annular or arciform pattern on the distal extremities. Although localized GA is most commonly observed, a generalized or disseminated form can occur. The etiology of GA is unknown; however, multiple inciting factors have been proposed. Histologically, GA is characterized by foci of degenerative collagen associated with palisading, sometimes infiltrating granulomatous inflammation. We report 6 cases with biopsy-proved GA, resistant to the standard modalities of treatment that resolved after 3 months with monthly rifampin (600 mg), ofloxacin (400 mg), and minocycline hydrochloride (100 mg) combination therapy. Rifampin, ofloxacin, and minocycline combination therapy has been successfully used to treat patients with paucibacillary leprosy. Given reports that prolonged antibiotic agents are a useful treatment for GA, rifampin (600 mg), ofloxacin (400 mg), and minocycline hydrochloride (100 mg) combination therapy was initiated in these patients. Complete clearance of the plaques was achieved 3 to 5 months after the initiation of treatment. Some patients experienced postinflammatory hyperpigmentation. Although our treatment was effective, further studies may be needed to confirm the success of this therapeutic option for patients with recalcitrant lesions of GA.

Confirmation of emergence of mutations associated with atovaquone-proguanil resistance in unexposed Plasmodium falciparum isolates from Africa

BackgroundIn vitro and in vivo resistance of Plasmodium falciparum to atovaquone or atovaquone-proguanil hydrochloride combination has been associated to two point mutations in the parasite cytochrome b (cytb) gene (Tyr268Ser and Tyr268Asn). However, little is known about the prevalence of codon-268 mutations in natural populations of P. falciparum without previous exposure to the drug in Africa.MethodsThe prevalence of codon-268 mutations in the cytb gene of African P. falciparum isolates from Nigeria, Malawi and Senegal, where atovaquone-proguanil has not been introduced for treatment of malaria was assessed. Genotyping of the cytb gene in isolates of P. falciparum was performed by PCR-restriction fragment length polymorphism and confirmed by sequencing.Results295 samples from Nigeria (111), Malawi (91) and Senegal (93) were successfully analyzed for detection of either mutant Tyr268Ser or Tyr268Asn. No case of Ser268 or Asn268 was detected in cytb gene of parasites from Malawi or Senegal. However, Asn268 was detected in five out of 111 (4.5%) unexposed P. falciparum isolates from Nigeria. In addition, one out of these five mutant Asn268 isolates showed an additional cytb mutation leading to a Pro266Thr substitution inside the ubiquinone reduction site.ConclusionNo Tyr268Ser mutation is found in cytb of P. falciparum isolates from Nigeria, Malawi or Senegal. This study reports for the first time cytb Tyr268Asn mutation in unexposed P. falciparum isolates from Nigeria. The emergence in Africa of P. falciparum isolates with cytb Tyr268Asn mutation is a matter of serious concern. Continuous monitoring of atovaquone-proguanil resistant P. falciparum in Africa is warranted for the rational use of this new antimalarial drug, especially in non-immune travelers.

IMMOBILIZATION OF FREE-RANGING MANED WOLF (CHRYSOCYON BRACHYURUS) WITH TILETAMINE AND ZOLAZEPAM IN CENTRAL BRAZIL

A tiletamine hydrochloride-zolazepam hydrochloride combination was used successfully to immobilize 27 free-ranging maned wolves (Chrysocyon brachyurus) at a mean dose of 2.77+/-0.56 (mean+/-SD) mg/kg. The induction time ranged from 3-15 min. Animals remained immobilized for periods of 48.56 +/-12.65 min. Compulsive licking, excessive salivation, muscle twitching, muscle tremors, tachypnea, and bradycardia were observed associated with the induction of the anesthesia in 13 of 27 maned wolves. Muscle twitching, pedal withdrawal reflex, muscle tremors, and ataxia were observed during recovery in three (11%) maned wolves. There were no significant differences in heart rates (P = 0.44), respiratory rates (P = 0.82), and rectal temperatures (P = 0.54) recorded at 5, 15, and 25 min after induction at these dosages. The tiletamine hydrochloride-zolazepam hydrochloride combination was shown to be an effective and safe immobilizing agent for free-ranging maned wolves.

Combination Chemotherapy With Irinotecan Hydrochloride (CPT-11) and Mitomycin C in Platinum-Refractory Ovarian Cancer

The aim of this study was to examine the level of activity of irinotecan hydrochloride (CPT-11) and mitomycin-C (MMC) combination chemotherapy in a patient population with platinum-refractory ovarian cancer. Patients received CPT-11 (140 mg/m2) in combination with MMC (7 mg/m2) on days 1, 15, 29 until disease progression, unacceptable toxicity developed, or they elected to discontinue treatment. Overall, 61 cycles of CPT-11/MMC chemotherapy were delivered to 13 patients. The major toxicity with this regimen was neutropenia, which was brief and reversible. The incidences of grade 3 and 4 neutropenia were 46% (6/13) and 15% (2/13), respectively. The nonhematological toxicities were generally mild and well tolerated. Of the 13 patients, 4 (31%) experienced an objective response (1 CR, 3 PRs). Among responders, the median duration of response was 30 weeks (range, 12 to 292+ weeks). The median time to progression for the 13 patients who received treatment on this trial was 24 weeks (range, 8 to 292+ weeks), with a median survival of 36 weeks (range, 20 to 292+ weeks). This preliminary study shows that the combination of CPT-11 and MMC appears to be an active regimen in patients with refractory ovarian cancer.

Immobilisation of impala (Aepyceros melampus) with a ketamine hydrochloride/medetomidine hydrochloride combination, and reversal with atipamezole hydrochloride.

A combination of medetomidine hydrochloride (medetomidine) and ketamine hydrochloride (ketamine) was evaluated in 16 boma-confined and 19 free-ranging impalas (Aepyceros melampus) to develop a non-opiate immobilisation protocol. In free-ranging impala a dose of 220 +/- 34 microg/kg medetomidine and 4.4 +/- 0.7 mg/kg ketamine combined with 7500 IU of hyaluronidase induced recumbency within 4.5 +/- 1.5 min, with good muscle relaxation, a stable heart rate and blood pH. PaCO2 was maintained within acceptable ranges. The animals were hypoxic with reduced oxygen saturation and low PaO2 in the presence of an elevated respiration rate, therefore methods for respiratory support are indicated. The depth of sedation was adequate for minor manipulations but additional anaesthesia is indicated for painful manipulations. Immobilisation was reversed by 467 +/- 108 microg/kg atipamezole hydrochloride (atipamezole) intramuscularly, but re-sedation was observed several hours later, possibly due to a low atipamezole:medetomidine ratio of 2:1. Therefore, this immobilisation and reversal protocol would subject impalas to possible predation or conspecific aggression following reversal if they were released into the wild. If the protocol is used on free-ranging impala, an atipamezole:medetomidine ratio of 5:1 should probably be used to prevent re-sedation.

Rosiglitazone maleate/metformin hydrochloride: A new formulation therapy for type 2 diabetes

Many patients with type 2 diabetes require treatment with more than one antihyperglycemic drug to achieve optimal glycemic control. The thiazolidinediones are a novel class of oral antihyperglycemic drugs that improve glycemic control primarily by increasing peripheral insulin resistance and sensitizing the skeletal muscle, liver and adipose tissue to the actions of insulin, in addition to improving beta-cell function. One of the many features of the thiazolidinedione class of drugs is their synergism with other antihyperglycemic drugs that have a different mechanism of action. The combination of metformin hydrochloride, a biguanide that enhances glucose uptake in peripheral tissues and reduces hepatic gluconeogenesis, with rosiglitazone maleate, one of the newly available members of the thiazolidinedione family, offers a rational therapeutic approach to the treatment of type 2 diabetes. In patients whose type 2 diabetes is inadequately controlled with metformin monotherapy, the addition of rosiglitazone significantly improves glycemic control, insulin sensitivity and beta-cell function, compared with either drug alone. In addition, this combination therapy has beneficial effects on other cardiovascular risk factors. Rosiglitazone maleate/metformin hydrochloride combination therapy is well tolerated in patients with type 2 diabetes and has a favorable safety profile. This review summarizes the available evidence on the clinical efficacy and safety of rosiglitazone maleate and metformin hydrochloride combination therapy in patients with type 2 diabetes.

Pharmacokinetic properties of single-dose loratadine and ambroxol alone and combined in tablet formulations in healthy men

Background: Due to Mexico's complicated socioeconomic environment, causing a high occurrence of >1 person sharing a single room, respiratory conditions are spread easily. Respiratory conditions are the main reason for consultation with a physician. The most frequent symptoms are throat soreness and cough; therefore, a new formulation combining loratadine and ambroxol hydrochloride was designed to treat these 2 major symptoms. The combination is expected to provide relief when coprescribed with more specific therapies, such as antibiotics. Objective: This study determined the pharmacokinetic profile of single-dose loratadine-ambroxol hydrochloride combination therapy versus each component given separately. The analyses included descarboethoxyloratadine (DCL), the primary active metabolite of loratadine. Methods: This was a 4-week, single-center, randomized, open-label, 3-period crossover study in adult male volunteers aged 18 to 50 years and in good general health. Subjects were randomized to receive single doses of treatment A (2 loratadine 5-mg tablets + ambroxol 30-mg tablets), B (2 ambroxol 30-mg tablets), or C (1 loratadine 10-mg tablet) in 1 of 3 sequences (ABC, BCA, or CAB) per period. A 14-day washout period separated each treatment period. Plasma concentration-time data curves for each subject and treatment were analyzed by noncompart-mental methods to obtain values for area under the curve (AUC), maximum plasma concentration (C max), and time to reach C max (T max)- Results: Thirty subjects (mean [SD] age, 22.5 [2.6] years) were enrolled. All treatments were well tolerated. Formulations A and C produced similar loratadine and DCL AUC from time 0 to 24 hours (AUC 0−24) values, but showed slightly high C max. values for loratadine and slightly low C max values for DCL, indicating failure to demonstrate bioinequivalence. Formulations A and B produced similar ambroxol C max, T max, and AUC 0−24 values. Conclusions: In this population of healthy mate volunteers, results showed the bioavailability of loratadine and ambroxol from the new formulation and did not show impairment of absorption when the drugs were formulated in a combination tablet.

Dimethyl dimethoxy biphenyl dicarboxylate and amantadine hydrochloride combination in treatment of chronic hepatitis C a pilot study in Egypt

Dimethyl dimethoxy biphenyl dicarboxylate and amantadine hydrochloride combination in treatment of chronic hepatitis C a pilot study in Egypt

Stability-indicating HPLC assays for the determination of prilocaine and procaine drug combinations

Stability-indicating, reversed phase high-performance liquid chromatographic (HPLC) methods have been developed for the determination of several procaine hydrochloride and prilocaine hydrochloride combinations. The separation and quantitation of epinephrine–prilocaine and epinephrine–procaine drug combinations were achieved on a phenyl column using a mobile phase of 80:20% v/v 25 mM phosphate buffer (pH 3.0) containing 50 mM heptanesulfonic acid sodium salt–acetonitrile at a flow rate of 1 ml min −1 and UV detection at 254 nm. The method showed linearity for the epinephrine and prilocaine hydrochloride mixture in the 0.25–2.5 and 8–200 μg ml −1 ranges, respectively. The intra- and inter-day relative standard deviations (RSDs) ranged from 0.26 to 2.05% and 0.04 to 0.61% for epinephrine and prilocaine hydrochloride, respectively. The epinephrine and procaine hydrochloride mixture yielded linear ranges of 0.25–2.0 and 5–100 μg ml −1 and intra- and inter-day RSDs ranged from 0.23 to 1.88% and 0.07 to 0.26% for epinephrine and procaine hydrochloride, respectively. The assays were shown to be suitable for measuring epinephrine–prilocaine and epinephrine–procaine combinations in their respective injection dosage forms. Stability-indicating HPLC assays were also developed for several other procaine drug combinations since their monographs are present in the USP 24; however, quantitation was not investigated since these combinations are not commercially available. A mobile phase consisting of 80:20% v/v 25 mM phosphate buffer (pH 3.0) containing 50 mM heptanesulfonic acid–acetonitrile was utilized for the levonordefrin–tetracaine–procaine drug combination, while a mobile phase consisting of 70:30% v/v 25 mM phosphate buffer (pH 3.0) containing 50 mM heptanesulfonic acid sodium salt–acetonitrile was utilized for the separation of levonordefrin–procaine–propoxycaine and norepinephrine–procaine–propoxycaine. All separations were achieved on a phenyl column at a flow rate of 1 ml min −1 and UV detection at 254 nm.