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Biomedical subjects

T P Kanyok

Publications and source records attributed to T P Kanyok.

9 recordsLinked to original sources
PubMed2000

Early bactericidal activity of paromomycin (aminosidine) in patients with smear-positive pulmonary tuberculosis.

The early bactericidal activity of the aminoglycoside paromomycin (aminosidine) in doses of 7.5 and 15 mg/kg of body weight was measured in 22 patients with previously untreated smear-positive pulmonary tuberculosis. The fall in log(10) CFU per milliliter of sputum per day during the first 2 days of treatment for 7 patients receiving a paromomycin dosage of 7.5 mg/kg/day was 0.066, with a standard deviation (SD) of 0.216 and confidence limits from -0.134 to 0.266, and that for 15 patients receiving 15 mg/kg/day was 0.0924, with an SD of 0.140 and confidence limits from 0.015 to 0.170. The difference between the mean and zero was not significant for the 7. 5-mg/kg dose group but was significant for the 15-mg/kg dose group (t = 2.55, P = 0.023). Since paromomycin has no cross-resistance with streptomycin and has no greater toxicity than other aminoglycosides, these results suggest that it has the potential to substitute for streptomycin in antituberculosis regimens and may be a particularly valuable addition to the drug armamentarium for the management of multidrug-resistant tuberculosis.

Adolescent↗
PubMed1999

In-vitro synergy of paromomycin with metronidazole alone or metronidazole plus hydroxymetronidazole against Helicobacter pylori.

The in-vitro activities of paromomycin and metronidazole alone or paromomycin and metronidazole plus hydroxymetronidazole (2:1 ratio) were studied against 19 Helicobacter pylori isolates using an in-vitro chequerboard technique. Partial synergy was demonstrated for the majority of isolates (11/19) for both combinations tested. When hydroxymetronidazole was added to the parent compound, the number of metronidazole-sensitive isolates demonstrating synergy increased to 5/12, compared with 1/12 for the combination that did not include the metabolite. In metronidazole-resistant isolates there was a shift from an additive effect to partial synergy for the combination containing hydroxymetronidazole. The in-vitro activity of paromomycin and the synergic effect that is achieved in combination with metronidazole and hydroxymetronidazole render paromomycin suitable for further investigation as a treatment option for H. pylori infection.

Anti-Bacterial Agents↗
PubMed1998

Randomised controlled trial of aminosidine (paromomycin) v sodium stibogluconate for treating visceral leishmaniasis in North Bihar, India.

OBJECTIVES: To assess the efficacy and tolerability of aminosidine compared with sodium stibogluconate for treating visceral leishmaniasis. DESIGN: Randomised, unblinded, controlled trial with 180 day follow up. SETTING: Kala-Azar Research Centre, Brahmpura, Muzaffarpur, Bihar, India. SUBJECTS: People of either sex aged 6-50 years with symptoms and signs suggestive of visceral leishmaniasis (fever, loss of appetite, enlarged spleen) with leishmania amastigotes detected in Giemsa stained aspirates of spleen or bone marrow. INTERVENTIONS: Aminosidine at three daily doses (12, 16, and 20 mg/kg) for 21 days and sodium stibogluconate 20 mg/kg/day for 30 days. MAIN OUTCOME MEASURES: Laboratory measures of efficacy: parasite count, haemoglobin concentration, white cell count, platelet count, serum albumin concentration. Clinical measures of efficacy: spleen size, fever, body weight, and liver size. Measures of safety: liver and renal function tests, reports of adverse events. RESULTS: Of the 120 patients enrolled (30 per treatment arm), 119 completed treatment and follow up. Cure at end of follow up was achieved in 23 (77%), 28 (93%), and 29 (97%) patients treated with 12, 16, and 20 mg aminosidine/kg/day respectively, and in 19 (63%) patients given sodium stibogluconate. At 16 and 20 mg/kg/day, aminosidine was significantly more active than sodium stibogluconate in both clinical and laboratory measures of efficacy. No significant clinical or laboratory toxicity occurred in any treatment group. CONCLUSIONS: A 21 day course of aminosidine 16 or 20 mg/kg/day should be considered as first line treatment for visceral leishmaniasis in Bihar.

Adolescent↗
PubMed1997

Pharmacokinetics of intramuscularly administered aminosidine in healthy subjects.

Aminosidine is an older, broad-spectrum aminoglycoside antibiotic that has been shown to be effective in in vitro and animal models against multiple-drug-resistant tuberculosis and the Mycobacterium avium complex. The objective of this randomized, parallel trial was to characterize the single-dose pharmacokinetics of aminosidine sulfate in healthy subjects (eight males, eight females). Sixteen adults (mean [+/- standard deviation] age, 27.6 +/- 5.6 years) were randomly allocated to receive a single, intramuscular aminosidine sulfate injection at a dose of 12 or 15 mg/kg of body weight. Serial plasma and urine samples were collected over a 24-h period and used to determine aminosidine concentrations by high-performance liquid chromatographic assay. A one-compartment model with first-order input, first-order output, and a lag time (Tlag) and with a weighting factor of 1/y2 best described the data. Compartmental and noncompartmental pharmacokinetic parameters were estimated with the microcomputer program WinNonlin. One subject was not included (15-mg/kg group) because of the lack of sampling time data. On average, subjects attained peak concentrations of 22.4 +/- 3.2 microg/ml at 1.34 +/- 0.45 h. All subjects had plasma aminosidine concentrations below 2 microg/ml at 12 h, and all but two subjects (one in each dosing group) had undetectable plasma aminosidine concentrations at 24 h. The dose-adjusted area under the concentration-time curve from 0 h to infinity of aminosidine was identical for the 12- and 15-mg/kg groups (9.29 +/- 1.5 versus 9.29 +/- 2.2 microg x h/ml per mg/kg; P = 0.998). Similarly, no significant differences (P > 0.05) were observed between dosing groups for peak aminosidine concentration in plasma, time to peak aminosidine concentration in plasma, Tlag, apparent clearance, renal clearance, elimination rate constant, and elimination half-life. A significant difference was observed for the volume of distribution (0.35 versus 0.41 liters/kg; P = 0.037) between the 12 and 15 mg/kg dosing groups. Now that comparable pharmacokinetic profiles between dosing groups have been demonstrated, therapeutic equivalency testing via in vitro pharmacokinetic and pharmacodynamic modelling and randomized clinical trials in humans should be conducted.

Adult↗
PubMed1994

In vivo activity of paromomycin against susceptible and multidrug-resistant Mycobacterium tuberculosis and M. avium complex strains.

Encouraged by in vitro results, we have assessed the in vivo activity of paromomycin (PRM) against Mycobacterium tuberculosis, multidrug-resistant (MDR) M. tuberculosis (resistant to isoniazid, rifampin, and streptomycin), and Mycobacterium avium complex in C57BL/6 mice and their beige counterparts. In all these experiments, PRM was effective in preventing mortality from a mycobacterial infection and was significantly more active than the drug-free control (P < 0.0005) in reducing the CFU relative to the mean log CFU in the lungs, livers, and spleens of infected animals. In the drug-susceptible M. tuberculosis experiment, PRM given at 100 and 200 mg/kg of body weight was significantly less active than isoniazid at 25 mg/kg (P < 0.0005) in reducing the mean log CFU in the lungs, livers, and spleens of infected mice. In the MDR M. tuberculosis experiment, PRM given at 200 mg/kg was effective, relative to the drug-free control, in reducing the mean log CFU of an isolate of M. tuberculosis resistant to isoniazid, rifampin, and streptomycin. In the M. avium complex experiment, PRM given at 200 mg/kg was as effective as amikacin at 50 mg/kg in reducing the mean log CFU in the lungs, livers, and spleens of infected mice. On the basis of our experiments, we believe that PRM has promising activity in vivo in the treatment of infections caused by M. tuberculosis, MDR M. tuberculosis, and M. avium complex.

Animals↗
PubMed1993

Treatment of cryptosporidial diarrhea in an AIDS patient with paromomycin.

OBJECTIVE: To report a case of diarrhea caused by Cryptosporidium in an AIDS patients which was successfully treated with paromomycin. CASE SUMMARY: An AIDS patient with a 12-month history of cryptosporidial diarrhea unresponsive to other treatment measures was treated with paromomycin 500 mg q6h for 14 days. Before initiating therapy, the patient was experiencing, on average, 20 bowel movements per day and had lost more than 25 kg. After therapy was initiated, the number of bowel movements dropped to 1-2 per day and the patient began to gain weight. The diarrhea recurred when therapy was discontinued. After retreatment for 14 days with paromomycin 500 mg q6h, the diarrhea stopped. The patient has not had a recurrence of Cryptosporidium diarrhea, stool cultures remain negative for Cryptosporidium oocysts, and the patient has regained most of the weight. DISCUSSION: Literature concerning the use of paromomycin for the treatment of cryptosporidiosis is discussed. A treatment algorithm for the management of cryptosporidiosis in AIDS patients is presented. CONCLUSIONS: We believe that we have presented a clear example of a case in which paromomycin was effective in treating and eradicating intestinal cryptosporidiosis in an AIDS patient. Paromomycin is the most effective agent available to date for the treatment of this devastating complication of AIDS.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

A prospective randomized, comparative, open-label trial of the safety and efficacy of paromomycin (aminosidine) plus sodium stibogluconate versus sodium stibogluconate alone for the treatment of visceral leishmaniasis.

Response to treatment with organic pentavalent antimonials, the standard first-line treatment for visceral leishmaniasis (VL), has been decreasing since their introduction into India. Combining sodium stibogluconate (SB) with paromomycin (PM) may be an efficient alternative to single-agent therapy. This trial was designed to assess the safety and efficacy of PM 12 or 18 mg/kg daily plus SB 20 mg/kg daily for 21 days compared to SB alone for 30 days. One hundred and fifty patients were randomly assigned in 1996 to 1 of the 3 treatments and followed-up for 180 days. At the end of treatment, 49 of 52 patients receiving PM12 + SB, 46 of 48 receiving PM18 + SB, and 27 of 49 patients receiving SB alone, were cured. During follow-up there was 1 relapse in each of the treatment groups, giving final cure rates of 48 of 52 (92.3%) for PM12 + SB, 45 of 48 (93.8%) for PM18 + SB, and 26 of 49 (53.1%) for SB. PM plus SB for 21 days at either 12 or 18 mg/kg daily was significantly more effective than SB alone for 30 days (chi 2 P < 0.001). One patient (SB alone) had experienced a serious adverse event: cardiotoxicity at day 8 (myocarditis and ECG changes) which caused withdrawal from the study. Only 19 of 100 patients enrolled in the PM treatment arms had a complete audiogram series conducted thus making it difficult to assess oto-toxicity. PM 12 or 18 mg/kg daily plus a standard dose of SB for 21 days was statistically more effective than SB in producing a final cure for patients with VL in Bihar, India.

Adolescent↗