A randomized controlled trial (volunteer study) of sitafloxacin, enoxacin, levofloxacin and sparfloxacin phototoxicity

Dawe, Robert; Ibbotson, S.H.; Sanderson, J. B.; Thomson, E.M.; Ferguson, J.

doi:10.1111/j.1365-2133.2003.05582.x

Cited by 78 publications

(45 citation statements)

References 26 publications

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“…The better efficacy of these drugs over CIP appears to be somewhat complex, involving higher MPCs, better pharmacokinetics, and better intramacrophage penetration (71). There are other FQs with lower MICs for tuberculosis, often with a methoxy group at the C 8 position (66), but some of the most active were found to be too toxic for widespread use: sitafloxacin and sparfloxacin are phototoxic (19), and the promising FQ gatifloxacin (GAT) caused problems with hypoglycemia and hyperglycemia, especially in older patients (93). That left moxifloxacin (MOX) as the best hope for an expanded FQ role in treatment of TB (29), although clinical trials are still ongoing with GAT (38) (see Table 2).…”

Section: Fqs Play An Important Role In the Treatment Of Mdr Tbmentioning

confidence: 99%

Current Prospects for the Fluoroquinolones as First-Line Tuberculosis Therapy

Takiff

Guerrero

2011

Antimicrob Agents Chemother

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While fluoroquinolones (FQs) have been successful in helping cure multidrug-resistant tuberculosis (MDR TB), studies in mice have suggested that if used as first-line agents they might reduce the duration of therapy required to cure drug-sensitive TB. The results of phase II trials with FQs as first-line agents have been mixed, but in at least three studies where moxifloxacin substituted for ethambutol, there was an increase in the early percentage of sputa that converted to negative for bacilli. Phase III trials are in progress to test the effectiveness of 4-month FQ-containing regimens, but there is concern that the widespread use of FQs for other infections could engender a high prevalence of FQ-resistant TB. However, several studies suggest that despite wide FQ use, the prevalence of FQ-resistant TB is low, and the majority of the resistance is low-level. The principal risk for resistance may be when FQs are used to treat nonspecific respiratory symptoms that are in fact TB, so curtailing this use of FQs could reduce the development of resistance and also the delays in TB diagnosis and treatment that have been documented when an FQ is given in this setting. While the future of FQs as first-line therapy will likely depend upon the results of the ongoing phase III trials, if they are to be effectively employed in high-TB-burden regions their use for community-acquired pneumonias should be restricted, the prevalence of FQ-resistant TB should be monitored, and the cost of the treatment should be comparable to that of current standard drug regimens.There are two main problems with tuberculosis (TB) chemotherapy, and the fluoroquinolones (FQs) may be able to help with both. First, although the total duration of treatment has been reduced from 18 to 24 months to 6 months by the systematic use of rifampin (RIF) and pyrazinamide, such a 6-month duration is still very long for patients and burdensome for health services in numerous countries where TB is highly endemic and can lead to the second problem, the development of strains resistant to the drugs. The success of the fluoroquinolone antibiotics in treating strains that are resistant to the standard first-line drugs has led to the suggestion that if used as first-line therapy they may be able shorten the duration of treatment. However, excitement over this possibility is tempered by the fear that their widespread community use for other infections will engender a high prevalence of FQ-resistant TB strains in the population. FQs: HIGH HOPES BUT ALSO HIGH RATES OF RESISTANCEThe quinolones are synthetic molecules that got their start when nalidixic acid was discovered in 1962 (47) and then introduced into clinical use in 1967 for the treatment of Gramnegative urinary tract infections (26). The addition of a fluorine atom significantly increased their antibacterial activity, and by adding various side groups literally thousands of different fluoroquinolones were synthesized. Although the increased broad-spectrum activity of ciprofloxacin (CIP) created the expectation ...

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Section: Fqs Play An Important Role In the Treatment Of Mdr Tbmentioning

confidence: 99%

Current Prospects for the Fluoroquinolones as First-Line Tuberculosis Therapy

Takiff

Guerrero

2011

Antimicrob Agents Chemother

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“…Both of these phototoxins have been well defined as both preclinical and clinical literature that document their clinical and mechanistic background based on visual observation. For example, the publications that established preclinical photosafety testing (e.g., Sambuco et al 1984), as did work ranking the relative clinical photosafety risk of fluoroquinolones (Dawe et al 2003 (2003) photosafety guidance documents, do not mention histopathologic evaluation as part of either preclinical or clinical assessment of phototoxic skin, further argues against the use of histopathologic evaluations for safety assessments intended for regulatory submissions. While the omission of histopathological end points from these guidance documents does not preclude their use, the results reported here provide a scientific basis that inclusion of histopathologic evaluation of the skin for safety assessment purposes does not provide information over that provided by clinical observation.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous Phototoxicity

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Elliott

2016

Toxicol Pathol

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Determination of test material-induced cutaneous phototoxicity for risk assessment has traditionally been based on visually observed skin reactions such as erythema, edema, and flaking. Because of its role in determining a toxic effect, the use of histopathological evaluation in this determination arises from time to time. However, there is little published information regarding the time course and types of histopathologic changes in the skin after test material-induced phototoxic insult nor any regulatory requirement or precedent for its use. This work evaluated both the visual and histopathological time course of the phototoxic response of the skin of the Long-Evans rat after oral administration of the phototoxins sparfloxacin and 8-methoxypsoralen (MOP) followed by a single exposure to solar-simulated ultraviolet radiation. Both sparfloxacin and 8-MOP elicited visual cutaneous reactions and microscopic changes consistent with a phototoxic response. The visually observed cutaneous time course and elicited histopathologic changes differed in response and extent for each phototoxin, but in both instances, microscopic evaluation did not alter the determination of a phototoxic response based on visual observations. These results indicate that, though histopathologic evaluations may have value for investigating mechanisms of phototoxicity, histopathologic evaluation of the skin is not warranted for determination of phototoxic potential in safety assessment intended for regulatory submission.

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“…Zwrócono jednak uwagę na fakt, że fluorochinolony ze znaczną aktywnością przeciwbakteryjną ujawniały zbyt dużo działań ubocznych, niekiedy toksycznych, np. : sitafloksacyna, sparfloksacyna i gatifloksacyna [68,69].…”

Section: Fluorochinolony W Leczeniu Gruźlicyunclassified

Lewofloksacyna i moksyfloksacyna w leczeniu zakażeń bakteryjnych

Płusa¹

2016

Forum Zakażeń

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STRESZCZENIE: Klasyfikacja fluorochinolonów została oparta na spektrum mikrobiologicznym i cechach farmakokinetycznych kolejno wprowadzanych preparatów, które charakteryzowały się lepszymi właściwościami farmakodynamicznymi, w tym znaczną penetracją do wnę-trza makrofagów i miejsca toczącego się procesu zapalnego. Przeprowadzona porównaw-cza analiza lewofloksacyny i moksyfloksacyny wskazuje na ich skuteczność kliniczną w kontrolowaniu zakażeń układowych zarówno w obrębie układu oddechowego, jak i moczowego, zwłaszcza w przypadku lewofloksacyny. Z tego powodu obydwa preparaty znalazły się w obowiązujących obecnie rekomendacjach postępowania w zakażeniach. Narastająca oporność na antybiotyki zmusza do ich racjonalnego stosowania -zgodnego ze światowymi wytycznymi.SŁOWA KLUCZOWE: lewofloksacyna, moksyfloksacyna, zakażenie ABSTRACT: Classification of fluoroquinolones is based on the spectrum of microbiological and pharmacokinetic characteristics in turn introduced preparations, which were characterized by improved pharmacodynamic properties, including significant penetration into the macrophages and inflammatory tissue. Conducted a comparative analysis of levofloxacin and moxifloxacin indicates clinically effective in controlling systemic infections both within the respiratory tract and urinary tract, particularly levofloxacin. For this reason, two products had been included in the recommendations of conduct infections developed in recent years. Increasing antibiotic resistance forces to their rational use -in accordance with international guidelines. WSTĘP Wskazaniem do stosowania antybiotyków są stany zapalne wywołane przez drobnoustroje. W zależności od rodzaju patogenu, jego aktywności i wrażliwości na podawany preparat o działaniu hamującym rozwój lub zabijającym bakterie, uzyskuje się odpowiedni efekt kliniczny. Najważniej-szym elementem tego postępowania, poza charakterystyką patogenu, są cechy farmakokinetyczne stosowanego antybiotyku, w tym: jego spektrum działania, stopień penetracji do miejsca toczącego się procesu zapalnego, wykazywane interakcje z innymi cząsteczkami oraz bezpieczeństwo dla chorego [1]. Posiadana wiedza w tym zakresie jest bardzo pomocna przy podejmowaniu decyzji terapeutycznych. KLASYFIKACJA FLUOROCHINOLONÓWChinolony należą do czynników przeciwbakteryjnych zsyntetyzowanych w latach 60. XX wieku w wyniku modyfikacji podstawowej dwupierścieniowej chemicznej struktury. Współczesna klasyfikacja fluorochinolonów jest oparta na spektrum mikrobiologicznym i cechach farmakokinetycznych poszczególnych preparatów. Należy podkreślić, Artyku jest dost pny na zasadzie dozwolonego u ytku osobistego. Dalsze rozpowszechnianie (w tym umieszczanie w sieci) jest zabronione i stanowi powa ne naruszenie przepisów prawa autorskiego oraz grozi sankcjami prawnymi.

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A randomized controlled trial (volunteer study) of sitafloxacin, enoxacin, levofloxacin and sparfloxacin phototoxicity

Cited by 78 publications

References 26 publications

Current Prospects for the Fluoroquinolones as First-Line Tuberculosis Therapy

Current Prospects for the Fluoroquinolones as First-Line Tuberculosis Therapy

Cutaneous Phototoxicity

Lewofloksacyna i moksyfloksacyna w leczeniu zakażeń bakteryjnych

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