Prevent custom field from being updated after first publish

You are updating the audio_url regardless of one was found in the content or not.
Make it conditional: 

if(preg_match_all ( "/(http|https):\/\/.*\/(.*)\.(mp3|m4a|ogg|wav|wma)/", $post->post_content, $matches )) {
    update_post_meta( $post_id, 'audio_url', $matches[0][0] ); 
}

In this case, you could also use preg_match, because you’re only looking for a single instance.

Also make sure that your regex does work correctly. Right now, it would get you wrong results if two URLs are in the document, since “.*” is greedy and will match as much as possible. Add a ? to change that behaviour to non-greedyness. While we’re at it, let’s remove the need to escape every Slash by using different delimiters:

"!(http|https)://.*?/(.*?)\.(mp3|m4a|ogg|wav|wma)!"

You don’t really need the parentheses around that second .*?, but maybe you have more code that needs it? Also, (http|https) could be written as https?, the question mark makes the previous character optional.

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