the new combination is especially directed to the treatment of gastropathies e . g . induced by helicobacter pylori infections . helicobacter pylori is a gram - negative spirilliform bacterium which colonises in the gastric mucosa . treatment with commonly used acid degradable antibiotics alone has given insufficient effect . the combination of 5 - methoxy - 2 -([( 4 - methoxy - 3 , 5 - dimethyl - 2 - pyridinyl ) methyl ] sulfinyl )- 1h - benzimidazole ( generic name : omeprazole ) or pharmaceutically acceptable salts thereof and an acid degradable antibiotic give an especially high plasma concentration of the antibiotic following oral administration . the salt of omeprazole according to the invention is an alkaline pharmaceutically acceptable salt . examples of such salts include inorganic salts , such as alkali metal salts , e . g . sodium salt , potassium salt etc ., alkaline earth metal salts , e . g . calcium salt , magnesium salt etc ., ammonium salt , organic salts such as organic amine salts , e . g . trimethylamine salt , triethylamine salt , pyridine salt , procaine acid , picoline salt , dicyclohexylamine salt , n , n - dibenzylethylenediamine salt , n - methylglucamine salt , diethanolamine salt , triethanolamine salt , tris ( hydroxymethylamino ) methane salt , phenylethylbenzylamine salt , dibenzylethylenediamine salt . also other proton pump inhibitors , such as lansoprazole may be used according to the invention . the antibiotic used in the combination should be of the kind , which has a bioavailability which may be improved due to elevation of intragastric ph . it should also be an antimicrobial compound with a very narrow spectrum e . g . benzylpenicillin . other examples are acid degradable and acid semi - stable macrolides e . g . erythromycin base and clarithromycin ( nakagawa et al ., chem . pharm . bull ., 1992 , 40 , 725 - 28 ). further examples are antibiotics and / or salts thereof which are pharmaceutically enginered for acid protection like for instance enteric coating ( e . g . ery - max ®). the antibacterial activity against helicobacter pylori as indicated by mic - values of macrolides is drastically decreased with increased ph of the medium in vitro ( melanoski et al ., icaac , 1992 , abstract 713 , p 229 ). the combination according to the present invention can be produced in one pharmaceutical formulation comprising both active ingredients or in two separate tablets or capsules , powder , mixture , effervescence tablets or solution . the active ingredients according to the invention are administered in the form of a pharmaceutical preparation containing the active ingredients as such ( e . g . the free base in the case of erythromycin ) or in the case of omeprazole also as a salt thereof in combination with a pharmaceutically acceptable carrier by the oral or parenteral route . the carrier mentioned above may be a solid , semi - solid or liquid diluent or a capsule . compatible dosage forms include various types of tablets , capsules , granules , powders , oral liquids , injections and so on . the proportions of the active ingredient in the total composition is generally 0 . 1 to 100 weight percent and preferably 0 . 1 to 95 weight precent . in the manufacture of a pharmaceutical preparation for oral administration , the active ingredient can be formulated with a solid particulate carrier such as lactose , sucrose , sorbitol , mannitol , starch , amylopectin , a cellulose derivative or gelatin , and a lubricating agent such as magnesium stearate , calcium stearate or polyethylene glycol wax may be further incorporated . the resulting composition is then compressed into tablets . coated tablets or dragees can be manufactured by coating the core tablets , thus prepared , with a thick sugar solution containing gum arabic , gelatin , talc , titanium dioxide , etc . or a lacquer prepared using a volatile organic solvent or solvent mixture . soft gelatin capsules can be manufactured by filling a composition comprising the active ingredient and a known vegetable oil into capsules . hard gelatin capsules can be manufactured by filling into capsules the granules or pellets each comprising the active ingredient and a solid particulate carrier such as lactose , sucrose , sorbitol , mannitol , potato starch , corn starch , amylopectin , a cellulose derivative or gelatin . the dosage of omeprazole or a salt thereof and the antibiotic depends on individual needs ( for example , the patient &# 39 ; s condition , body weight , age , sex , etc .) as well as on the method of administration . generally speaking , the oral dosage may range from 1 to 200 mg of omeprazole per day and up to 10 g of acid degradable antibiotic per adult human . each may be administered in one to a few divided doses . benzylpenicillin was administered alone to eight healthy volunteers and in combination with omeprazole and the plasma concentration was measured . when benzylpenicillin was administered alone the plasma concentrations , which were expressed in terms of the area under the plasma concentration - time curve , auc ( mg - h / l ), and the maximum concentration , c max ( mg / l ), and time , t , or maximum time , t max ( h or min ), were insufficient for a therapeutical effect ( table 1 ). when benzylpenicillin was combined with omeprazole therapeutical useful plasma concentrations were reached ( table 2 ). similar results were obtained after oral administration of erythromycin lactobionate prior and after omeprazole induced reduction of acid secretion in man ( tables 3 and 4 ). semidegradable macrolides , e . g . ery - max ® and clarithromycin are absorbed to a certain extent ( tables 5 and 7 ). however , after administration of an acid secretion inhibitor , omeprazole , a marked increase of the bioavailability of the macrolides is shown as indicated by the difference in c max and auc in healthy volunteers ( tables 6 and 8 ). compare also fig1 and fig2 showing the accurate plasma concentrations of ery - max ® and clarithromycin with and without omeprazole . the high plasma concentrations of the antibiotics after reduction of the gastric acid secretion is evidence for a great reduction of the degradation in the stomach of the antibiotics used . this results in an increased amount of the active antibiotic in the gastric lumen , thus resulting in increased local antimicrobial effect . it also leads to a larger amount of the antibiotic available for absorption , thus resulting in increased plasma and tissue levels of the antibiotic ( increased bioavailability ). the best mode of carrying out the invention at present is to combine omeprazole with erythromycin . table 1__________________________________________________________________________concentration in plasma of benzylpenicillin after oral administrationdose 1 . 0 g . ( without omeprazole ) personplasma concentration mg / l cmax aucnumber15 &# 39 ; 30 &# 39 ; 45 &# 39 ; 1 h 1 . 5 h 2 h 3 h 4 h 6 h mg / l h · mg / l__________________________________________________________________________1 0 . 24 0 . 50 0 . 54 0 . 41 0 . 22 0 . 135 0 . 074 & lt ; 0 . 02 & lt ; 0 . 02 0 . 54 0 . 812 0 . 53 1 . 60 1 . 47 1 . 24 0 . 52 0 . 30 0 . 14 0 . 063 & lt ; 0 . 02 1 . 60 2 . 063 0 . 23 0 . 51 0 . 45 0 . 37 0 . 21 0 . 11 0 . 051 0 . 016 & lt ; 0 . 02 0 . 51 0 . 694 0 . 076 0 . 23 0 . 20 0 . 15 0 . 084 0 . 053 0 . 044 0 . 023 & lt ; 0 . 02 0 . 23 0 . 385 0 . 26 0 . 50 0 . 41 0 . 40 0 . 28 0 . 17 0 . 071 0 . 042 & lt ; 0 . 02 0 . 50 0 . 846 0 . 33 0 . 37 0 . 26 0 . 20 0 . 099 0 . 051 0 . 038 & lt ; 0 . 02 & lt ; 0 . 02 0 . 37 0 . 487 0 . 17 0 . 26 0 . 23 0 . 17 0 . 14 0 . 075 0 . 027 & lt ; 0 . 02 & lt ; 0 . 02 0 . 26 0 . 398 0 . 104 0 . 125 0 . 124 0 . 121 0 . 062 0 . 050 0 . 021 & lt ; 0 . 02 & lt ; 0 . 02 0 . 125 0 . 24mean 0 . 24 0 . 51 0 . 46 0 . 38 0 . 20 0 . 118 0 . 058 & lt ; 0 . 03 & lt ; 0 . 02 0 . 52 0 . 74value ± s . d . 0 . 46 0 . 58__________________________________________________________________________ cmax : tdep = 4 . 163 p & lt ; 0 . 01 auc : tdep = 5 . 553 p & lt ; 0 . 001 table 2__________________________________________________________________________concentration in plasma of benzylpenicillin after oral administrationdose 1 . 0 g . ( with omeprazole ) personplasma concentration mg / l cmax aucnumber15 &# 39 ; 30 &# 39 ; 45 &# 39 ; 1 h 1 . 5 h 2 h 3 h 4 h 6 h mg / l h · mg / l__________________________________________________________________________1 0 . 89 2 . 98 3 . 25 3 . 41 3 . 74 2 . 79 0 . 89 0 . 70 0 . 25 3 . 74 9 . 542 0 . 73 2 . 80 5 . 51 5 . 74 2 . 26 1 . 62 0 . 84 0 . 76 0 . 28 5 . 74 9 . 523 1 . 40 6 . 24 9 . 85 9 . 75 6 . 59 1 . 67 0 . 53 0 . 30 0 . 061 9 . 85 13 . 204 0 . 11 0 . 72 1 . 22 3 . 05 7 . 57 5 . 59 2 . 94 0 . 45 0 . 094 7 . 57 12 . 805 0 . 64 2 . 48 2 . 45 2 . 10 1 . 95 1 . 10 0 . 46 0 . 25 0 . 054 2 . 48 4 . 826 1 . 24 3 . 22 3 . 65 3 . 57 1 . 42 0 . 84 0 . 55 0 . 33 0 . 074 3 . 65 5 . 787 0 . 33 0 . 83 1 . 43 1 . 52 1 . 17 0 . 87 0 . 45 0 . 21 0 . 074 1 . 52 3 . 348 0 . 62 1 . 37 2 . 31 2 . 35 2 . 54 1 . 37 0 . 48 0 . 23 0 . 041 2 . 54 5 . 00mean 0 . 745 2 . 58 3 . 71 3 . 94 3 . 41 1 . 98 0 . 89 0 . 40 0 . 116 4 . 64 8 . 00value ± s . d . 2 . 87 3 . 79__________________________________________________________________________ cmax : tdep = 4 . 163 p & lt ; 0 . 01 auc : tdep = 5 . 553 p & lt ; 0 . 001 table 3__________________________________________________________________________concentration in plasma of erythromycin lactobionate after oral ainistration . dose 1 . 0 g . 1 ( 2 ) without preceding omeprazole treatmentsubjectsserum levels in mg / l at indicated timesnumber0 15 &# 39 ; 30 &# 39 ; 45 &# 39 ; 1 h 1 . 5 h 2 h 3 h 4 h 6 h__________________________________________________________________________1 & lt ; 0 . 015 0 . 015 0 . 15 0 . 29 0 . 28 0 . 20 0 . 18 0 . 13 0 . 091 0 . 0472 & lt ; 0 . 015 0 . 26 0 . 33 0 . 30 0 . 25 0 . 25 0 . 18 0 . 15 0 . 16 0 . 0703 & lt ; 0 . 015 0 . 042 0 . 22 0 . 21 0 . 24 0 . 14 0 . 13 0 . 12 0 . 86 0 . 0494 & lt ; 0 . 015 0 . 032 0 . 042 0 . 030 0 . 039 0 . 078 0 . 084 0 . 076 0 . 072 0 . 0465 & lt ; 0 . 015 0 . 023 0 . 13 0 . 16 0 . 16 0 . 15 0 . 14 0 . 12 0 . 082 0 . 0516 & lt ; 0 . 015 0 . 068 0 . 12 0 . 094 0 . 11 0 . 098 0 . 077 0 . 074 0 . 059 0 . 0347 & lt ; 0 . 015 0 . 57 0 . 98 0 . 75 0 . 68 0 . 43 0 . 37 0 . 32 0 . 27 0 . 0888 & lt ; 0 . 015 0 . 071 0 . 27 0 . 33 0 . 23 0 . 16 0 . 16 0 . 12 0 . 095 0 . 044mean & lt ; 0 . 015 0 . 135 0 . 28 0 . 27 0 . 25 0 . 18 0 . 165 0 . 14 0 . 11 0 . 054value ± s . d . ± 0 . 193 ± 0 . 30 ± 0 . 22 ± 0 . 19 ± 0 . 11 ± 0 . 092 ± 0 . 078 ± 0 . 070 ± 0 . 017__________________________________________________________________________ table 3__________________________________________________________________________concentration in plasma of erythromycin lactobionate after oraladministration . dose 1 . 0 g . 2 ( 2 ) with preceding omeprazole treatmentsubjectserum levels in mg / l at indicated timesnumber0 15 &# 39 ; 30 &# 39 ; 45 &# 39 ; 1 h 1 . 5 h 2 h 3 h 4 h 6 h__________________________________________________________________________1 & lt ; 0 . 015 2 . 9 7 . 5 7 . 6 7 . 2 4 . 9 4 . 0 3 . 1 3 . 5 1 . 42 & lt ; 0 . 015 2 . 3 6 . 8 5 . 7 4 . 5 5 . 3 3 . 6 3 . 3 3 . 2 1 . 43 & lt ; 0 . 015 2 . 7 12 . 7 10 . 9 7 . 8 6 . 0 5 . 3 4 . 5 4 . 0 2 . 44 & lt ; 0 . 015 3 . 2 6 . 0 3 . 3 2 . 5 1 . 9 2 . 8 2 . 4 2 . 4 0 . 825 & lt ; 0 . 015 0 . 25 2 . 8 6 . 4 4 . 8 3 . 0 2 . 5 2 . 0 2 . 8 1 . 26 & lt ; 0 . 015 1 . 5 4 . 9 3 . 4 2 . 7 1 . 6 1 . 8 1 . 6 2 . 1 0 . 897 & lt ; 0 . 015 6 . 3 9 . 8 9 . 3 6 . 2 5 . 3 4 . 6 4 . 6 3 . 9 1 . 88 & lt ; 0 . 015 3 . 8 12 . 8 13 . 0 11 . 1 10 . 7 7 . 3 5 . 6 4 . 3 2 . 2mean & lt ; 0 . 015 2 . 87 7 . 91 7 . 45 5 . 85 4 . 84 3 . 99 3 . 39 3 . 28 1 . 51value ± s . d . ± 1 . 77 ± 3 . 60 ± 3 . 46 ± 2 . 86 ± 1 - 2 . 89 ± 1 . 76 ± 1 . 40 ± 0 . 79 ± 0 . 58__________________________________________________________________________ table 4______________________________________kinetic data following oral administration ( s ) oferythromycin lactobionate to 8 healthy volunteers with andwithout co - administration of omeprazole . a cross over study . c . sub . max t . sub . max auc mg / l h h · mg / lomeprazole mean ± sd median 0 - 6 h______________________________________yes 8 . 38 ± 0 . 28 0 . 5 21 . 74 ± 8 . 64no 0 . 32 ± 0 . 28 0 . 75 0 . 83 ± 0 . 55______________________________________ table 5__________________________________________________________________________blood serum levels of erythromycin ery - max ® following oraladministration . dose 500 mg . 1 ( 2 ) without preceding omeprazole treatment . subjectserum levels in mg / l at indicated times ( min ) number0 30 60 90 120 150 180 300 480 720__________________________________________________________________________1 0 . 00 0 . 06 0 . 06 0 . 06 0 . 12 0 . 28 1 . 90 0 . 76 0 . 15 0 . 062 0 . 00 0 . 06 0 . 06 0 . 06 0 . 06 0 . 06 0 . 06 0 . 65 0 . 19 0 . 063 0 . 00 0 . 06 0 . 06 0 . 06 0 . 06 0 . 08 0 . 75 0 . 49 0 . 20 0 . 064 0 . 00 0 . 06 0 . 06 0 . 06 0 . 06 0 . 16 0 . 43 0 . 92 0 . 25 0 . 075 0 . 00 0 . 06 0 . 06 0 . 06 0 . 06 0 . 25 0 . 95 1 . 50 0 . 45 0 . 076 0 . 00 0 . 06 0 . 06 0 . 06 0 . 06 0 . 06 0 . 06 0 . 52 0 . 17 0 . 067 0 . 00 0 . 06 0 . 10 0 . 38 0 . 41 0 . 68 1 . 10 0 . 46 0 . 20 0 . 068 0 . 00 0 . 06 0 . 06 0 . 06 0 . 51 1 . 20 1 . 70 0 . 86 0 . 31 0 . 06mean 0 . 00 0 . 06 0 . 07 0 . 10 0 . 17 0 . 35 0 . 87 0 . 77 0 . 24 0 . 06sdev 0 . 00 0 . 00 0 . 01 0 . 11 0 . 18 0 . 40 0 . 69 0 . 34 0 . 10 0 . 01__________________________________________________________________________ table 5__________________________________________________________________________blood serum levels of erythromycin ery - max ® following oraladministration . dose 500 mg . 2 ( 2 ) without preceding omeprazole treatment . auc levels at indicated times ( min ) subject totnumber0 30 m 60 m 90 m 120 m 150 m 180 m 300 m 480 m 720 m auc__________________________________________________________________________1 0 0 . 015 0 . 03 0 . 03 0 . 045 0 . 1 0 . 545 2 . 66 1 . 365 0 . 42 5 . 212 0 0 . 015 0 . 03 0 . 03 0 . 03 0 . 03 0 . 03 0 . 71 1 . 26 0 . 5 2 . 6353 0 0 . 015 0 . 03 0 . 03 0 . 03 0 . 036 0 . 208 1 . 24 1 . 035 0 . 52 3 . 1444 0 0 . 015 0 . 03 0 . 03 0 . 03 0 . 055 0 . 148 1 . 35 1 . 755 0 . 646 4 . 0595 0 0 . 015 0 . 03 0 . 03 0 . 03 0 . 078 0 . 3 2 . 45 2 . 925 1 . 036 6 . 8946 0 0 . 015 0 . 03 0 . 03 0 . 03 0 . 03 0 . 03 0 . 58 1 . 035 0 . 46 2 . 247 0 0 . 015 0 . 04 0 . 12 0 . 198 0 . 273 0 . 445 1 . 56 0 . 99 0 . 52 4 . 168 0 0 . 015 0 . 03 0 . 03 0 . 143 0 . 428 0 . 725 2 . 56 1 . 755 0 . 74 6 . 425mean 0 0 . 015 0 . 031 0 . 041 0 . 067 0 . 129 0 . 304 1 . 639 1 . 515 0 . 605sdev 0 0 . 015 0 . 004 0 . 032 0 . 066 0 . 145 0 . 25 0 . 827 0 . 647 0 . 202__________________________________________________________________________ auc : 4 . 34 ± 1 . 7 c . sub . max : 1 . 005 table 6__________________________________________________________________________blood serum levels of erythromycin ery - max ® following oraladministration . dose 250 mg . 1 ( 2 ) with preceding omeprazole treatment . subjectserum levels in mg / l at indicated times ( min ) number0 30 m 60 m 90 m 120 m 150 m 180 m 300 m 480 m 720 m__________________________________________________________________________1 0 . 00 0 . 06 0 . 54 3 . 2 2 . 4 2 . 3 1 . 9 0 . 79 0 . 22 0 . 062 0 . 00 0 . 06 0 . 06 0 . 1 0 . 69 2 . 1 1 . 7 0 . 54 0 . 14 0 . 063 0 . 00 0 . 06 0 . 29 1 . 2 2 . 5 2 . 5 1 . 4 0 . 75 0 . 23 0 . 064 0 . 00 0 . 06 0 . 06 0 . 094 0 . 84 0 . 74 0 . 37 1 . 3 0 . 45 0 . 0815 0 . 00 0 . 06 0 . 06 0 . 059 0 . 58 1 . 5 1 . 7 1 . 6 0 . 5 0 . 0846 0 . 00 0 . 06 0 . 068 0 . 49 1 . 2 0 . 86 0 . 68 0 . 48 0 . 14 0 . 067 0 . 00 0 . 06 0 . 057 1 . 1 1 . 3 2 2 . 1 0 . 87 0 . 27 0 . 0878 0 . 00 0 . 06 0 . 48 1 . 4 1 . 9 1 . 6 1 . 7 1 0 . 28 0 . 084mean 0 . 00 0 . 06 0 . 20 0 . 96 1 . 43 1 . 7 1 . 44 0 . 92 0 . 28 0 . 07sdev 0 . 00 0 . 00 0 . 21 1 . 06 0 . 76 0 . 65 0 . 61 0 . 38 0 . 13 0 . 01__________________________________________________________________________ table 6__________________________________________________________________________blood serum levels of erythromycin ery - max ® following oraladministration . dose 250 mg . 2 ( 2 ) with preceding omeprazole treatment . auc levels at indicated times ( min ) subject totnumber0 30 m 60 m 90 m 120 m 150 m 180 m 300 m 480 m 720 m auc__________________________________________________________________________1 0 . 00 0 . 015 0 . 15 0 . 935 1 . 4 1 . 175 1 . 05 2 . 69 1 . 515 0 . 56 9 . 492 0 . 00 0 . 015 0 . 03 0 . 04 0 . 198 0 . 698 0 . 95 2 . 24 1 . 02 0 . 4 5 . 593 0 . 00 0 . 015 0 . 088 0 . 373 0 . 925 1 . 25 0 . 975 2 . 15 1 . 47 0 . 58 7 . 8254 0 . 00 0 . 015 0 . 03 0 . 039 0 . 234 0 . 395 0 . 278 1 . 67 2 . 625 1 . 062 6 . 3475 0 . 00 0 . 015 0 . 03 0 . 03 0 . 16 0 . 52 0 . 8 3 . 3 3 . 15 1 . 168 9 . 1736 0 . 00 0 . 015 0 . 032 0 . 14 0 . 423 0 . 515 0 . 385 1 . 16 0 . 93 0 . 4 3 . 9997 0 . 00 0 . 015 0 . 029 0 . 289 0 . 6 0 . 825 1 . 025 2 . 97 1 . 71 0 . 714 8 . 1878 0 . 00 0 . 015 0 . 0135 0 . 47 0 . 825 0 . 875 0 . 825 2 . 7 1 . 92 0 . 728 8 . 493mean 0 . 00 0 . 015 0 . 065 0 . 289 0 . 595 0 . 782 0 . 786 2 . 36 1 . 793 0 . 702sdev 0 . 00 0 . 00 0 . 052 0 . 31 0 . 434 0 . 312 0 . 295 0 . 703 0 . 764 0 . 284__________________________________________________________________________ auc : 7 . 38 ± 1 . 9 c . sub . max : 1 . 94 table 7__________________________________________________________________________blood serum levels of clarithromycin following oral administration . dose250 mg . 1 ( 2 ) without preceding omeprazole treatment . subjectserum levels in mg / l at indicated times ( min ) number0 30 m 60 m 90 m 120 m 150 m 180 m 360 m 660 m 840 m__________________________________________________________________________1 0 . 00 0 . 11 0 . 97 0 . 92 1 . 1 1 . 5 1 . 2 0 . 96 0 . 41 0 . 262 0 . 00 0 . 12 0 . 15 0 . 24 0 . 28 0 . 36 0 . 47 0 . 53 0 . 18 0 . 143 0 . 00 0 . 06 0 . 11 0 . 092 0 . 11 0 . 12 0 . 17 0 . 55 0 . 2 0 . 124 0 . 00 0 . 06 0 . 06 0 . 044 0 . 099 0 . 13 0 . 15 0 . 48 0 . 23 0 . 135 0 . 00 0 , 06 0 . 06 0 . 062 0 . 064 0 . 13 0 . 18 0 . 54 0 . 2 0 . 166 0 . 00 0 . 07 0 . 13 0 . 2 0 . 3 0 . 37 0 . 45 0 . 23 0 . 14 0 . 0827 0 . 00 0 . 12 0 . 26 0 . 27 0 . 46 0 . 81 0 . 78 0 . 64 0 . 2 0 . 128 0 . 00 0 . 06 0 . 31 0 . 38 0 . 41 0 . 55 0 . 57 0 . 64 0 . 27 0 . 16mean 0 . 00 0 . 08 0 . 26 0 . 28 0 . 35 0 . 50 0 . 50 0 . 57 0 . 23 0 . 15sdev 0 . 00 0 . 03 0 . 30 0 . 28 0 . 34 0 . 47 0 . 36 0 . 20 0 . 08 0 . 05__________________________________________________________________________ table 7__________________________________________________________________________blood serum levels of clarithromycin following oral administration . dose250 mg . 2 ( 2 ) without preceding omeprazole treatment . auc levels at indicated times ( min ) subject totnumber0 30 m 60 m 90 m 120 m 150 m 180 m 360 m 660 m 840 m auc__________________________________________________________________________1 0 . 00 0 . 028 0 . 27 0 . 473 0 . 505 0 . 65 0 . 675 2 . 16 4 . 11 1 . 005 9 . 8952 0 . 00 0 . 03 0 . 068 0 . 098 0 . 13 0 . 16 0 . 208 1 2 . 13 0 . 48 4 . 3033 0 . 00 0 . 015 0 . 043 0 . 051 0 . 051 0 . 058 0 . 073 0 . 72 2 . 25 0 . 48 3 . 7394 0 . 00 0 . 015 0 . 03 0 . 026 0 . 036 0 . 057 0 . 07 0 . 63 2 . 13 0 . 54 3 . 5345 0 . 00 0 . 015 0 . 03 0 . 031 0 . 032 0 . 049 0 . 078 0 . 72 2 . 22 0 . 54 3 . 7136 0 . 00 0 . 018 0 . 05 0 . 083 0 . 125 0 . 168 0 . 205 0 . 68 1 . 11 0 . 333 2 . 7717 0 . 00 0 . 03 0 . 095 0 . 133 0 . 183 0 . 318 0 . 398 1 . 42 2 . 52 0 . 48 5 . 5758 0 . 00 0 . 015 0 . 093 0 . 173 0 . 198 0 . 24 0 . 28 1 . 21 2 . 73 0 . 645 5 . 583mean 0 . 00 0 . 021 0 . 085 0 . 133 0 . 157 0 . 212 0 . 248 1 . 068 2 . 4 0 . 563sdev 0 . 00 0 . 007 0 . 079 0 . 146 0 . 154 0 . 201 0 . 207 0 . 525 0 . 838 0 . 199__________________________________________________________________________ auc : 4 . 88 ± 2 . 24 c . sub . max : 0 . 68 table 8__________________________________________________________________________blood serum levels of clarithromycin following oral administration . dose250 mg . 1 ( 2 ) with preceding omeprazole treatment . subjectserum levels in mg / l at indicated times ( min ) number0 30 60 90 120 150 180 360 660 840__________________________________________________________________________1 0 . 00 1 . 9 2 . 3 2 . 2 1 . 7 1 . 7 1 . 7 0 . 86 0 . 37 0 . 282 0 . 00 0 . 078 3 1 . 9 1 . 9 1 . 9 1 . 7 0 . 78 0 . 34 0 . 163 0 . 00 0 . 6 1 . 6 1 . 3 1 . 1 1 . 1 1 . 05 0 . 68 0 . 23 0 . 144 0 . 00 0 . 06 1 . 2 1 . 3 1 . 2 1 . 03 1 . 1 0 . 68 0 . 39 0 . 25 0 . 00 0 . 096 2 . 1 1 . 6 1 . 3 1 . 1 1 . 1 0 . 77 0 . 27 0 . 186 0 . 00 0 . 21 1 . 2 1 . 8 1 . 6 1 1 . 5 0 . 67 0 . 22 0 . 137 0 . 00 0 . 12 0 . 99 1 . 1 0 . 9 0 . 89 1 . 07 0 . 61 0 . 22 0 . 168 0 . 00 1 . 07 2 . 2 2 2 1 . 7 1 . 8 0 . 92 0 . 38 0 . 24mean 0 . 00 0 . 52 1 . 82 1 . 65 1 . 46 1 . 30 1 . 38 0 . 75 0 . 30 0 . 19sdev 0 . 00 0 . 66 0 . 69 0 . 39 0 . 40 0 . 39 0 . 33 0 . 11 0 . 08 0 . 05__________________________________________________________________________ table 8__________________________________________________________________________blood serum levels of clarithromycin following oral administration . dose250 mg . 2 ( 2 ) with preceding omeprazole treatment . auc levels at indicated times ( min ) subject totnumber0 30 60 90 120 150 180 360 660 840 auc__________________________________________________________________________1 0 . 00 0 . 475 1 . 05 1 . 125 0 . 975 0 . 85 0 . 85 2 . 56 3 . 69 0 . 975 12 . 552 0 . 00 0 . 02 0 . 77 1 . 225 0 . 95 0 . 95 0 . 9 2 . 48 3 . 36 0 . 75 11 . 43 0 . 00 0 . 15 0 . 55 0 . 725 0 . 6 0 . 55 0 . 538 1 . 73 2 . 73 0 . 555 8 . 1284 0 . 00 0 . 015 0 . 315 0 . 625 0 . 625 0 . 558 0 . 533 1 . 78 3 . 21 0 . 885 8 . 5455 0 . 00 0 . 024 0 . 549 0 . 925 0 . 725 0 . 6 0 . 55 1 . 87 3 . 12 0 . 675 9 . 0386 0 . 00 0 . 053 0 . 353 0 . 75 0 . 85 0 . 65 0 . 625 2 . 17 2 . 67 0 . 525 8 . 6457 0 . 00 0 . 03 0 . 278 0 . 523 0 . 5 0 . 448 0 . 49 1 . 68 2 . 49 0 . 57 7 . 0088 0 . 00 0 . 268 0 . 818 1 . 05 1 0 . 925 0 . 875 2 . 72 3 . 9 0 . 93 12 . 49mean 0 . 00 0 . 129 0 . 585 0 . 868 0 . 778 0 . 691 0 . 67 2 . 124 3 . 146 0 . 733sdev 0 . 00 0 . 165 0 . 275 0 . 251 0 . 192 0 . 191 0 . 174 0 . 416 0 . 499 0 . 18__________________________________________________________________________ auc : 9 . 7 ± 2 . 1 c . sub . max : 1 . 9 the advantage of the present combination of a compound that increases the intragastric ph , such as omeprazole and an acid degradable antibiotic , is that the bioavailability of the antibiotic will increase resulting in sufficient plasma levels for therapeutic effects . another advantage is that there will be increased amounts of the acid degradable antibiotic in the gastric lumen . benzylpenicillin is interesting because it has a very narrow spectrum and therefore exerts a very limited effect on the normal intestinal flora . by reducing the gastric acid secretion or acid neutralisation in the stomach the ph increases . due to the less acidic milieu the orally administered acid degradable antibiotic will be less catabolized and thus locally exerting its antimicrobial effect , another advantage is that increased amounts of the antibiotic will pass into the small intestine where it will be absorbed in biologically active form . increasing the intragastric ph is also favourable for antibiotic efficacy as shown in vitro . if the ph of the medium where helicobacter pylori is grown in vitro is reduced varying degrees below ph 7 the antibacterial properties rapidly decrease . those antibiotics which are weak bases e . g . macrolides will be excreted via the stomach wall due to its physico - chemical properties in congruence with other known weak bases i . e . nicotine , aminopurine and omeprazole ( larsson et al ., scand . j . gastroenterol ., 1983 , 85 , 900 - 7 ). thus , the antibiotic weak base will be biologically concentrated in the stomach wall , where the bacteria ( e . g . helicobacter pylori ) reside .
a synergistic pharmaceutical combination and composition are disclosed for the treatment of gastritis and peptic ulcer containing a therapeutic amount of a proton pump inhibitor such as e . g ., omeprazole or lansoprazole , which increases intragastric ph , and a therapeutic amount of an acid degradable antibacterial compound such as a penicillin or a macrolide . in particular , the combination is directed to the treatment of infections caused by helicobacter pylori by raising the bioavailability of acid degradable antibacterial compounds .